H1N1 INFLUENZA, El Huesped Diabolico II, Siete razones para no vacunarte !

Data-Medicos 
Dermagic/Express No.10-(X-18) 
11 November 2.009 /11 Noviembre 2.009

EDITORIAL ESPAÑOL                                                  
=================

H1N1 INFLUENZA, EL HUESPED DIABOLICO II, SIETE RAZONES PARA NO VACUNARTE!!

Quien fue, la persona que dijo por primera vez que se acercaba una guerra bacteriológica o virológica ?

1.) Scandals Poison Baxter H1N1 Vaccine Concerns

May 5th, 2009 • Category: Print Edition ShareThis
Steve Watson
Infowars.net
Thursday, April 30, 2009

Source:

http://www.thelibertyvoice.com/?p=760

A scandal dating from January 2008, that is continuing to unfold, raises more disturbing questions over the safety of U.S. pharmaceutical company Baxter International’s vaccines.
Last year Baxter recalled almost all of its injections of the blood thinning heparin drug in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, after being administered the products.
There were similar recalls by other manufacturers of Chinese-sourced heparin in Denmark, Italy, France Germany and Japan, but initial investigations found that only Baxter’s heparin vaccines were tainted.
Then, in January 2009 a new lawsuit was filed specifically against Baxter for it’s role in the scandal.
The allegation is that the pharmaceutical giant purposefully altered an ingredient in heparin that flowed through heparin syringes to patients, resulting in pain and suffering, and sometimes death, to those affected, reported legal website Lawyers and Settlements
Somewhat ironically, the natural ingredient in heparin that was substituted in order to cut costs was a substance extracted from cooked swine intestines.
Baxter has been chosen by the WHO to head up efforts to produce a vaccine for the Mexican swine flu that is spreading throughout the U.S. and Europe.
The decision was made despite further revelations last month that vaccines contaminated with deadly live H5N1 avian flu virus were recently distributed to 18 countries by a lab at an Austrian branch of Baxter.
Initially, the company attempted to stonewall questions by invoking “trade secrets” and refused to reveal how the vaccines were contaminated with H5N1. After increased pressure they then claimed that pure H5N1 batches were sent by accident.
However, the probability of mixing a live virus biological weapon with vaccine material by accident is virtually impossible.


2.) Proof H1N1 is Bioweapon as Baxter Files H1N1 Swine Flu Vaccine Patent a Year Ahead of Outbreak

Source:

http://www.fightbackh1n1.com/2009/08/proof-h1n1-is-bioweapon-as-baxter-files.html

New York :Baxter had patented vaccines for viruses that even don't exist a year back. This Clearly shows that the pandemic virus was not an act of nature.

The Primary Motive behind this alleged criminal activity is also the primary cause of most murders in the world today, and that motivation is simply: BIG MONEY. Billions of Dollars of windfall profits from government contracts worldwide, as a matter of fact
 

                                                           Patent                          

Direct link to USA patent website :

http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PG01&s1=20090060950&OS=20090060950&RS=20090060950

And yes the the Swine Flu virus H1N1 is listed "with many others" as copied from the Patent Application here at: [0056] "A vaccine can be used e.g. for an injection as a prophylactic means against a virus associated disease. In particular preferred embodiments the composition or vaccine comprises more than one antigen, e.g. 2, 3, 4, 5, 6, 7 or 8, in particular of different virus strains, subtypes or types such as influenza A and influenza B, in particular selected from of one or more of the human H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, H10N7 subtypes, of the pig flu H1N1, H1N2, H3N1 and H3N2 subtypes, of the dog or horse flu H7N7, H3N8 subtypes or of the avian H5N1, H7N2, H1N7, H7N3, H13N6, H5N9, H11N6, H3N8, H9N2, H5N2, H4N8, H10N7, H2N2, H8N4, H14N5, H6N5, H12N5 subtypes. "
Our additional concern is all the others virus vaccines listed but not yet promoted yet, get my point? !!
You may want to get this into a few specialists hands for comment immediately.
The following link is the most important. It shows that the original application was filed in 08/28/2007.
Start off from here http://portal.uspto.gov/external/portal/pair and when you get to the search page make sure "application number" is checked off and in the search field put in the application number of: 60/966,724
When it opens the page click on the tab "Image File Wrapper" then select "Specifications" and go to page "13" of the specifications. Here you will see the virus references to the viruses as noted above and it did so on "08/28/07" long before the virus was promoted as a "New and Deadly Strain" morphed out of a pig farm in Mexico

3.) Patent of the vaccine against virus H1N1 in the United States of America for the company Baxter.

Source:

http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PG01&s1=20090060950&OS=20090060950&RS=20090060950

The present invention provides a method for the manufacture of a preparation comprising virus antigens comprising a) inoculation of cells with infectious virus in a fluid, b) propagation of said virus in said cells, c) collecting said propagated virus, d) inactivating said collected virus, and e) treating said inactivated virus with a detergent, resulting in a preparation comprising viral antigens.

    BAXTER HEALTHCARE CORPORATION
    ONE BAXTER PARKWAY, DF2-2E
    DEERFIELD
    IL
    60015
    US

1. A method for the manufacture of a preparation comprising virus antigens comprisinga) inoculation of cells with infectious virus in a fluid,b) propagation of said virus in said cells,c) collecting said propagated virus,d) completely inactivating said collected virus, ande) treating said inactivated virus with detergent,resulting in a preparation comprising viral antigens.

2. The method of claim 1, wherein the step of collecting said propagated virus comprises separating the virus from said cells and/or cell debris of said cells after infection.

3. The method of 1, wherein said inactivation is performed by addition of formaldehyde.

4. The method of 1, wherein said inactivation is performed by UV irradiation.

5. The method of 1, wherein said propagated virus is released into said fluid.

6. The method of 1, wherein after the collection the collected fluid is treated with a nuclease.

7. The method of 6, wherein said nuclease is benzonase.

8. The method of claim 1, wherein said cells are in form of a cell culture during said virus propagation.

9. The method of claim 1, wherein said cells are mammalian or avian cells.

10. The method of claim 1, wherein said cells are epithelial cells.

11. The method of claim 8, wherein said cells are Vero cells.

12. The method of claim 1, wherein said virus is an enveloped virus

13. The method of claim 12, wherein said virus is an orthomyxo virus

14. The method of claim 13, wherein said virus is an influenza virus.

15. The method of claim 1, wherein the concentration of non-viral protein during said inactivation is below 350 .mu.g/ml.

16. The method of claim 1, wherein said manufacture is on industrial scale amounts.

17. The method of claim 16, wherein said inactivation is performed on at least 11 virus containing fluid.

18. A method for the manufacture of a preparation comprising viral antigens comprisinga) obtaining a fluid comprising infectious virus,b) inactivating said collected virus,c) treating said inactivated virus with detergent, andd) purifying said inactivated virus resulting in a preparation comprising viral antigens.

19. The method of claim 18, wherein said fluid is obtained from a cell culture.

20. The method of claim 19 further comprising the step of stabilizing said viral antigens.

21. The method of claim 20, wherein said viral antigens are stabilized by addition of an effective amount of Tween 80.

22. The method of claim 21, wherein Tween 80 is in an amount of about 0.125%.

23. A method of increasing the resistance to a viral infection in a subject comprising manufacturing a preparation comprising viral antigens by administering a preparation obtained by any one of the methods of claims 1-22 to a subject.

FIELD OF THE INVENTION

[0001]The present invention relates to methods for producing viral vaccines.

DESCRIPTION OF THE RELATED ART

[0002]A vaccine is an immunogenic composition of an antigenic substance, e.g. the (non-infectious) pathogen such as a virus, its envelope, particles or its protein antigens. Administration or vaccination results in the immunization in a subject, e.g. a mammal such as a human, or a bird. The vaccination might cause a specific reaction to the vaccine and some minor inflammation, but this is generally much less detrimental than an infection of a fully viable virus which the vaccine is designed to prevent. The immune system of the subjects will adapt itself to specifically recognize the antigens of the vaccine and swiftly inactivate the pathogen after further exposure of the subject to the pathogen. Thus an increased resistance against the pathogen is achieved through vaccination.

[0003]For vaccine purposes a virus is conventionally cultivated on an adequate cell culture or generally cellular substrate. In the case of influenza, normally embryonated chicken eggs are used. The infectious viral harvest is collected and purified to remove unwanted non-viral cell constituents. In particular, in the case of vaccines derived from chicken substrates allergic reaction to chicken/egg proteins are possible in certain susceptible individuals.

[0004]An essential step in the production of viral vaccines is the inactivation of the infectious viruses. Formalin (an aqueous solution of formaldehyde) is the most frequently used inactivating agent in the manufacture of vaccines. It is usually used as a saturated aqueous solution with concentration of around 37% formaldehyde. Formaldehyde inactivates a virus by irreversibly cross-linking primary amine groups in surface proteins with other nearby nitrogen atoms in protein or DNA through a --CH.sub.2-linkage. In particular these cross linkages could lead to bonds with non-viral substances and it is therefore necessary to perform some previous purification on the live infectious virus, since inactivation prior to purification would give rise to a large amount of irreversible chemical bridging between viral proteins and impurities, which are detrimental to the efficacy of the purification operations and product quality. For this reason, live infectious viruses are first at least partially purified in the prior art, e.g. by zonal ultracentrifugation, and then inactivated (U.S. Pat. No. 6,048,537). The formalin inactivation step has been validated with established analytical procedures.

[0005]Complementing formalin treatment, UV inactivation has been considered for integration into the manufacturing process. The use of ultraviolet irradiation-inactivation for human vaccines has been demonstrated before for unenveloped and enveloped virus (US 2006/0270017). As the viral genome is more susceptible to UV-damage than viral surface antigens, UV-inactivation was shown to have little negative effect on the biochemical characteristics or immunogenicity of the product. The targets for UV inactivation are primarily nucleic acids in contrast to proteins which are targeted by formalin.

[0006]By combining formalin and UV-inactivation, scientists tried to overcome the limitations of isolated UV-inactivation or formalin-inactivation, respectively, when inactivating particularly resilient virus families.

[0007]Alternatively, many manufacturers use a detergent-based process step to both inactivate the live virus and to modify the virus. These detergent-based processes disrupt the lipid envelope of influenza viruses to yield either split (partially disrupted) or sub-unit (fully disrupted) vaccine antigen. Detergent treatment often reduces the reactivity of the virus antigen, and thus reduces unwanted side effects during vaccination. The detergent treated virus may be further inactivated by, e.g., formalin treatment. Examples of these methods may be found in U.S. Pat. No. 6,048,573, U.S. Pat. No. 4,522,809, and WO 02/09702. A disadvantage in this approach is that the virus undergoes various purification steps prior to the disruption step, and thus live infectious virus is handled by manufacturing personnel at several stages. This is of especial concern when vaccine against especially virulent forms of influenza, such as H5N1 strains, is being produced.

SUMMARY OF THE INVENTION

[0008]It is an object of the present invention to provide a method of producing viral vaccines with a reduced number of steps requiring the handling of infectious material, while producing viral antigens of decreased reactivity.

[0009]Therefore the present invention provides a method for the manufacture of a preparation comprising virus antigens comprising

[0010]a) inoculation of cells with infectious virus in a fluid,

[0011]b) propagation of said virus in said cells,

[0012]c) collecting said propagated virus in the cell culture supernatant,

[0013]d) inactivating said collected virus, and

[0014]e) treating said inactivated virus with a detergent, resulting in a preparation comprising viral antigens.

[0015]In a second aspect a method for the manufacture of a preparation is provided comprising viral antigens comprising

[0016]a) obtaining a fluid comprising infectious virus,

[0017]b) completely inactivating said collected virus,

[0018]c) treating said inactivated virus with a detergent, and

[0019]d) purifying said inactivated virus resulting in a preparation comprising viral antigens.

[0020]Other aspects of the invention provide vaccine preparations prepared from the viral antigens produced according to the methods of the invention.

[0021]In another aspect the present invention provides the method of increasing the resistance to a viral infection in a subject comprising manufacturing a preparation comprising viral antigens and administering said preparation to a subject.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022]FIG. 1a shows a flow chart of the inventive procedure from virus collection after propagation to the inactivated harvest.

[0023]FIG. 1b shows a continuation of the flow chard of the inventive procedure from inactivated harvest to a monvalent bulk preparation.

DETAILED DESCRIPTION OF THE INVENTION

[0024]Provided is a method for the manufacture of a preparation comprising virus antigens comprising

[0025]a) inoculation of cells with infectious virus in a fluid,

[0026]b) propagation of said virus in said cells,

[0027]c) collecting said propagated virus in the cell culture supernatant,

[0028]d) completely inactivating said collected virus, and

[0029]e) treating said inactivated virus with a detergent, resulting in a preparation comprising viral antigens. Central to this procedure is that it is possible to reduce the number of steps performed on an active virus and thus the virus is inactivated after collection of the primary harvest prior to the detergent treatment and/or optional purification steps.

[0030]The "virus antigen" according to the present invention is a virus or portion of the virus which can induce an immune response in a subject against said antigen. Absolute success in the sense of completely immunising the subject is not required but this is to be understood in the sense of increasing the immune defence or immune response against said virus which reduces the chance of developing a disease associated with said virus after further exposure. Such a virus antigen can, e.g., be a whole inactivated virus, a split virus, a modified virus, viral proteins, in particular surface proteins, like haemagglutinin or neuraminidase. A "vaccine" is a preparation of said virus antigen in a form for administration, such as for injection, nasal, or transdermal administration. "Purification" according to the present invention relates to steps of removing non-viral constituents of the harvest fluid. The harvest fluid obtainable after the collection step is preferably a clarified supernatant, wherein solid or large impurities, e.g. remaining intact cells or cell debris of infected cells which break up during virus propagation, are removed by precipitation, e.g. via centrifugation. Therefore "collecting" refers to any steps that yield whole infectious viruses in a fluid, in particular clear fluid. Apart from removing cell debris the collection step can also include steps to remove other solid constituents of the cell growth medium or substrate e.g. any kind of substrate on which the cells are cultured. Propagated whole virus is released into said cell culture supernatant from which it can be collected. Therefore in a particular embodiment of the invention the step of collecting the propagated virus comprises separating the virus from the cells and/or cell debris of said cells after infection. This separation can, e.g., be facilitated by a low speed centrifugation of about 2000 g to 3000 g, up to 5000 g, 10000 g, 15000 g or 20000 g, which separates visible particles from the fluid. Alternately, the separation may be carried out by filtration. In particular preferred embodiments said fluid is substantially free of allantoin, collagen and/or albumin, such as ovalbumin, e.g. by choice of the cells used for virus propagation, e.g. mammalian, avian or insect cell cultures instead of embryonal eggs. In particular embodiments of the invention, African green monkey kidney (VERO) cells are used for viral propagation.

[0031]After the collecting step the virus is inactivated by any known means for virus inactivation, e.g. as disclosed in the US publication number 2006/0270017 A1, which is incorporated herein by reference. In particular, inactivation can be performed by formaldehyde treatment and/or UV irradiation, alone or in combination. As used in this application, "complete inactivation" or "completely inactivated," as they refer to a viral preparation, means that the viral preparation does not contain plaque forming units (pfu,) as determined by culture of the viral preparation on chicken embryonic fibroblasts (CEF) or VERO cells.

[0032]One of the beneficial effects of the inventive methods is the reduction of steps which are performed on infectious viral media for which specific safety precautions are required. In the state of the art it was considered to be necessary to perform a purification step on the primary harvest to remove or substantially reduce non-viral proteins or nucleic acids which could cross-link with the virus during formalin treatment. This prejudice was overcome with the present invention which showed that it is indeed possible or even advantageous to inactivate directly after collection of the virus prior to the purification. To avoid such adverse reaction during inactivation the virus containing fluid, or its non-viral constituents, is (are) preferably not further concentrated or concentrated by a factor of below 10, 9, 8, 7, 6, 5, 4, 3 or 2 during or after the collection step. Preferably the concentration of non-viral protein and/or DNA of the native supernatant from the cell culture is maintained prior to the inactivation step. In particular embodiments the whole protein or non-viral protein concentration is in the range of .mu.g/ml, such as below 950 .mu.g/ml, 900 .mu.g/ml, 850 .mu.g/ml, 800 .mu.g/ml, 700 .mu.g/ml, 650 .mu.g/ml, 600 .mu.g/ml, 550 .mu.g/ml, 500 .mu.g/ml, 450 .mu.g/ml, 400 .mu.g/ml, 350 .mu.g/ml, 300 .mu.g/ml, 250 .mu.g/ml, 200 .mu.g/ml, 150 .mu.g/ml, 100 .mu.g/ml, 80 .mu.g/ml, 60 .mu.g/ml, 40 .mu.g/ml, 30 .mu.g/ml, 20 .mu.g/ml, 10 .mu.g/ml, 8 .mu.g/ml, 6 .mu.g/ml, 4 .mu.g/ml, 3 .mu.g/ml, 2 .mu.g/ml or below 1 .mu.g/ml, in the fluid during inactivation or after collecting the virus.

[0033]For the inactivation any amount of formaldehyde or UV irradiation dosage can be selected which are effective to inactivate the virus, alone or in combination. In a preferred embodiment of the present application the virus titer reduction due to the inactivation of the virus in the sample is at least about 1.times.10.sup.5, in a more preferred embodiment, at least about 1.times.10.sup.7 in a more preferred embodiment at least about 1.times.10.sup.10, and in a most preferred embodiment at least about 1.times.10.sup.14.

[0034]In a preferred embodiment of the present invention, the sample is treated with an effective concentration of formalin for about 12 to about 96 hours. In more preferred embodiments, the sample is treated with an effective concentration of formalin for about 24 to about 48 hours, and more preferably for about 24 to about 30 hours. In an especially preferred embodiment of the present invention, the sample is treated with an effective concentration of formalin for about 24 to about 24.5 hours. Those of skill in the vaccine arts will recognize that formalin concentration and treatment times may need to be optimised for the particular strain of virus treated in order to effect complete inactivation, wither alone or in combination with UV light. In a further embodiment the step of treating the sample with an effective concentration of formalin is carried out at about 10 to about 40.degree. C. In an especially preferred embodiment of the pre-sent application the step of treating the sample with an effective concentration of formalin is carried out at about 32.degree. C.

[0035]A preferred embodiment of the present invention includes the treatment of the sample with an effective concentration of formalin, wherein the effective concentration of formalin ranges preferably from about 0.01% to about 1% (w/w), preferably from about 0.01% to about 0.1% more preferably between about 0.025% and about 0.1% which corresponds to about 92 mg/l and about 368 mg/l formalin respectively when using a 37% formalin solution for adjusting the effective concentration.

[0036]In the present application the term "UV light" means ultraviolet radiation having a wavelength of 100 to 400 nm. The UV light may be selected from the group consisting of UV C (100 to 280 nm), UV B (280 to 320 nm), and UV A (320 to 400 nm). Photosensitizing agents like those which intercalate into the DNA and are activated by UV light, e.g. psoralens, may be used to enhance the inactivating effect of the UV radiation. In a preferred embodiment of the present invention the UV light is UV C having a wavelength of about 100 to about 280 nm. In a more preferred embodiment of the present invention the UV light has a wavelength from about 240 to about 290 nm. In an especially preferred embodiment of the present invention about 85% or more of the UV light have a wavelength of about 254 nm.

[0037]The UV light emission may be a continuous form of UV light emission, e.g. mercury lamp technology, or pulsed UV light, e.g. monochromatic laser technology. The desired UV intensity may be generated by combining two or more lamps. The subject matter of the invention encompasses any effective dose of UV light, i.e. any dose of UV light which safely inactivates a given virus preferably when combined with a formalin treatment. Those of skill in the vaccine arts will recognize that UV light wavelength and exposure may need to be optimised for the particular strain of virus treated in order to effect complete inactivation, either alone or in combination with formalin treatment. The effective dose may depend on a variety of factors which are generally known in the field, e.g. the physical parameters of the UV inactivation chambers such as size and diameter of the lamp and the chamber, distance between the virus containing medium and the UV light source, light absorption and reflection properties of the material of the chamber. By the same token, the wavelength and intensity of the UV C light as well as the contact time the virus is exposed to the UV light is also critical for the effective dose. Furthermore, the effective dose is also influenced by the virus itself, the medium containing the virus and their light absorption properties. Preferably, the effective dose is sufficient for inactivating at least 99.99% of virus contained in the sample, more preferably inactivating the virus to a level where no active virus is detected in a mammalian or avian cell culture test, or completely inactivated. In a preferred embodiment using UV C light a sample containing the virus is exposed to an effective dose ranging from about 5 to about 200 mJ/cm.sup.2. In a preferred embodiment the effective dose is in the range of about 20 to about 100 mJ/cm.sup.2, and in other preferred embodiments the effective dose in the range of about 40 to about 90 mJ/cm.sup.2. In a preferred embodiment, the effective dose reduces an initial virus titer by 1.times.10.sup.5. In bulk vaccine inactivation, the effective dose should be sufficient to eliminate any residual live virus which may be present after the chemical (formalin) inactivation step. As illustrated in the examples, this may be determined by very sensitive mammalian cell culture infection tests, such as the Vero cell culture test described in Example 1.3.

[0038]After inactivation the virus antigens are purified. The purification is preferably performed by ultracentrifugation at e.g. in the range of about 100000 g such at least 50000 g, 60000 g, 70000 g, 80000 g, or 90000 g, or up to 200000 g, 180000 g, 160000 g, 140000, g 120000 g or 110000 g. The ultracentrifugation method is commonly known in the art and is used in the routine manufacture of viral vaccines as e.g. described in the U.S. Pat. No. 6,048,537, which is thus incorporated by reference. Preferably the ultracentrifugation is performed in a sucrose density gradient which establishes itself during the centrifugation. In particular preferred embodiments the sucrose gradient is formed by using a solution of about 42% to 55% (w/w-%) sucrose (or any other adequate carbohydrate or sugar known in the art). For ultracentrifugation a continuous flow centrifuge may be used. The parameters for fractionating after ultracentrifugation are dependent on the characteristics of the virus strains used. The parameters for collection of the peak pool fractions are evaluated and determined individually for each virus strain and are in the range of about 46-50% to 34-38% sucrose. Preferably non-viral material (e.g. at this stage whole inactivated virus) are removed by density separation. Cell membrane fragments, including liposomes and proteins each have a characteristic specific density. Viruses as being a characteristic composition of proteins, nucleic acids and in the case of enveloped viruses also membrane can be purified by their specific density from non-viral material. In particular the whole viral antigens may be purified from incomplete virus portions, or vice versa.

[0039]This step of purifying the inactivated virus comprises at least partially removing soluble non-viral material from the virus. In particular the soluble non-viral material comprises cell proteins or cell nucleic acids from the cell of the original cell medium or culture. Non-viral material, including incomplete virus portions, is preferably reduced by an amount of at least 20%, preferably at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% or at least 90% during purification.

[0040]In particular preferred embodiments the collected fluid is treated with a nuclease to degrade nucleic acids of the host cells. Such a nuclease can be e.g. benzonase.

[0041]In a further embodiment of the present invention, the cells use for cell culture and viral propagation may be primary cells or any cultured cell line suitable for producing the virus. Examples of cells which may be used include mammalian cells (e.g., CHO, BHK, VERO, HELA, or perC6 cells), avian cells (e.g, chicken embryo fibroblasts, or continuous cell lines from an avian) and insect cells (e.g, Sf9 cells.). In particular preferred embodiments the cells are in form of a cell culture. The inventive method allows effective purification, including splitting of the material despite of the potential cross linking properties of the previous inactivation reagents. In contrast to egg grown virus, cell culture derived virus is of higher initial purity and is free of albumin and collagens, which represents an important advantage for the purification of the formalin treated harvest. The innovative formulation of the resulting product is free of flocculation without any need for stabilizers such as tocopherol or laureth-9.

[0042]In the present invention, the viruses to be inactivated are selected from enveloped DNA or RNA viruses, with single or double (DNA) stranded genomes, sense or antisense, continuous or segmented. In preferred embodiments of the invention, the viruses are selected from the group of enveloped viruses, including, flaviviruses, togaviruses, retroviruses, coronaviruses, filoviruses, rhabdoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses, arenaviruses, hepadnaviruses, herpesviruses, and poxviruses. In other preferred embodiments, the viruses are flaviruses, coronaviruses, orthomyxoviruses, or togaviruses. Particularly preferred are enveloped viruses such as influenza, including strains of influenza A, B or C, West Nile, and Ross River viruses (RRV.) In other preferred embodiments of the invention, the viruses are selected from the group of enveloped RNA viruses, including, flaviviruses, togaviruses, retroviruses, coronaviruses, filoviruses, rhabdoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses, and arenaviruses. In one particularly preferred embodiment, the virus is selected from the orthomyxoviruses, for example, an influenza virus strain: influenza virus strains may have varying combinations of hemaglutianin and neuraminidase surface proteins. In another particularly preferred example, the virus is selected from the togaviruses, for example an alphavirus such as the RRV) Another preferred group of viruses for use as the bulk viral solution are the coronaviruses, including the virus associated with Severe Acute Respiratory Syndrome (SARS). Another group of preferred viruses are the flaviviruses, including Japanese Encephalitis, tick borne encephalitis (TBE), Dengue fever virus, yellow fevers virus, West Nile Virus and hemorrhagic fever virus. Another preferred group of viruses are the poxviruses, including orthopox-viruses (such as vaccinia or modified vaccinia Ankara viruses), and avipoxviruses.

[0043]In further embodiments the purified virus is further processed. After purification further steps can comprise dilution of the purified virus, in particular after sucrose ultracentrifugation in order to dilute the viscous peak pool fraction which is expected to contain about 40% sucrose. The purified virus can be homogenized, additionally nuclease treated, pressure and/or ultra/diafiltrated.

[0044]In embodiments of the invention, the virus is modified by detergent treatment to produce a modified whole virus or split virus vaccine. The modification of the lipid envelope of the virus is carried out by solubilisation with a detergent such as Triton X100 in a concentration suitable to destabilize or disintegrate the virus, in particular the viral lipid envelope membrane. The detergent treatment will at least in part remove the membrane of said virus. Preferably the detergent concentration is removed, e.g. by diafiltration or chromatographic processes. Detergents for use in the detergent treatment step include ionic (cationic, anionic, zwitterionic) detergents or non-ionic detergents. Suitable detergents include the Tween group of detergents (e.g., Tween 80), and the Triton group of detergents (e.g., Triton 100.)

[0045]Optionally, the viral antigen preparation is further stabilized by an additional formaldehyde treatment or stabilizer addition such as by usage of detergents as disclosed in the WO 02/097072 A2 which is incorporated herein by reference. Such detergents are for example detergents suitable to stabilize the HA protein, such as Tween 80, Triton X100, deoxycholate, laureth-9 and tocopherol. It is thought that surface proteins are kept solubilized by complex micelles of membrane constituents and the detergents.

[0046]In particular preferred embodiments the virus is further processed to a split virus comprising any one of the following steps of dilution, homogenisation, nuclease treatment, pressure filtration, ultra/diafiltration, solubilisation, diafiltration, stabilization by formaldehyde treatment, dilution, ultra/diafiltration, (detergent) stabilizer addition, a second homogenisation and sterile filtration.

[0047]In other particular preferred embodiments the virus is further processed to a modified virus preparation comprising any one of the following steps of dilution, homogenisation, nuclease treatment, pressure filtration, detergent treatment, ultra/diafiltration, stabilizer addition, a second homogenisation and sterile filtration. In particular the detergent stabilization is performed to introduce a detergent into the viral membrane in the case of enveloped virus to increase the stability of the complete virus, which is thus modified.

[0048]In additional embodiments the virus is processed to a sub-unit vaccine comprising the isolation of single viral subunits or viral proteins, in particular surface proteins like heamaggutinin or neuraminidase. The isolation can e.g. be performed by affinity purification and/or chromatographic methods such as ion exchange chromatography.

[0049]Surprisingly the method of the present invention is suitable for industrial scale production of virus antigen vaccines. Therefore preferably the inactivation or any other step such as the inoculation, the propagation the collection or the purification is performed on amounts or yields amounts of at least 0.51, 11, 21, 31, 41, 51 61, 71, 81, 91, 101, 121, 141, 161, 181, 201, 251, 301, 351, 401, 601, 801, 1001, 1201, 1401, 1601, 1801, 2001 of a fluid comprising a virus or viral antigen.

[0050]In a further aspect the present invention also provides a method for the manufacture of a preparation comprising viral antigens comprising

[0051]a) obtaining a fluid comprising infectious virus,

[0052]b) completely inactivating said collected virus,

[0053]c) treating said inactivated virus with a detergent,

[0054]d) purifying said inactivated virus resulting in a preparation comprising viral antigens. Of course it is also possible to use infectious virus containing fluids per se, which can be from any cell supernatant as described above, for inactivation, detergent treatment, and purification. Preferably said fluid comprising infectious virus is obtained from a cell culture.

[0055]In particular preferred embodiments the virus antigens, in particular split virus or modified virus antigens, are stabilized by addition of an effective amount of Tween 80, in particular preferred at a concentration of about 0.125%, e.g. above 0.01%, 0.05% or 0.4%, and below 0.6%, 0.5%, 0.4%, 0.3%, or 0.2%. Therefore the present invention also provides in a further aspect the method of stabilizing viral antigens by addition of Tween 80. According to the present invention it was found that as a detergent Tween 80 is less potent to solubilize viral membranes as Triton X100 but is by far more biocompatible and can be present in a vaccine preparation. The effective amount to stabilize viral antigens is preferably below the amount to solubilize viral membranes as in the split virus solubilization procedure using high concentrations of Triton X100 of e.g. 0.5%. In other embodiments the viral antigens are free of stabilizers. In particular embodiments a production of a split vaccine is provided by a process where the virus harvest is fully inactivated prior to the splitting and purification process. Surprisingly, the inactivation process with formalin treatment and UV treatment does not interfere with the subsequent detergent treatment and purification processes.

[0056]In further embodiments a vaccine or pharmaceutical composition is provided which comprises one or more viral antigens. Such a pharmaceutical composition can further comprise a pharmaceutical carrier and/or an adjuvant. Such pharmaceutical carriers are for example stabilising salts, emulgators, solubilisers or osmo-regulators, suspending agents, thickening agents, redox components maintaining a physiological redox potential. Pre-ferred adjuvants include aluminium salts, microemulsions, lipid particles, and/or oligonucleotides used to increase the immune response. A further aspect of the present invention is a pharmaceutical composition or preparation as vaccine comprising an antigen. A vaccine can be used e.g. for an injection as a prophylactic means against a virus associated disease. In particular preferred embodiments the composition or vaccine comprises more than one antigen, e.g. 2, 3, 4, 5, 6, 7 or 8, in particular of different virus strains, subtypes or types such as influenza A and influenza B, in particular selected from of one or more of the human H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, H10N7 subtypes, of the pig flu H1N1, H1N2, H3N1 and H3N2 subtypes, of the dog or horse flu H7N7, H3N8 subtypes or of the avian H5N1, H7N2, H1N7, H7N3, H13N6, H5N9, H11N6, H3N8, H9N2, H5N2, H4N8, H10N7, H2N2, H8N4, H14N5, H6N5, H12N5 subtypes.

[0057]Suitable adjuvants can be selected from mineral gels, aluminium hydroxide, surface active substances, lysolecithin, pluronic polyols, polyanions or oil emulsions such as water in oil or oil in water, or a combination thereof. Of course the selection of the adjuvant depends on the intended use. E.g. toxicity may depend on the destined subject organism and can vary from no toxicity to high toxicity.

[0058]Another preferred embodiment of the composition or vaccine of the present invention further comprises buffer substances. Buffer substances can be selected by the skilled artisan to establish physiological condition in a solution of the composition according to the invention. Properties like pH and ionic strength as well as ion content can be selected as desired.

[0059]A further preferred composition or vaccine according to the invention, comprises a pharmaceutically acceptable carrier.

[0060]The term "carrier" refers to a diluent, e.g. water, saline, excipient, or vehicle with which the composition can be administered. For a solid composition the carriers in the pharmaceutical composition may comprise a binder, such as microcrystalline cellulose, polyvinylpyrrolidone (polyvidone or povidone), gum tragacanth, gelatine, starch, lactose or lactose monohydrate; a disintegrating agent, such as alginic acid, maize starch and the like; a lubricant or surfactant, such as magnesium stearate, or sodium lauryl sulphate; a glidant, such as colloidal silicon dioxide; a sweetening agent, such as sucrose or saccharin.

[0061]Also provided is the method of increasing the resistance to a viral infection in a subject comprising manufacturing a preparation comprising one or more different viral antigens and administering said a preparation comprising one or more viral antigens as described above to a subject. The preparation is preferably a vaccine. It is also contemplated to provide the virus antigens as prepared by the present invention as a vaccine or for increasing the resistance to a viral infection in a subject by administering said virus antigens.

EXAMPLES

Example 1

Inactivation of Infectious Virus

[0062]Three different influenza strains, two A-strains Hiroshima (HR, H3N2), a New Calcdonia (NC, H1N1) and a B-strain, Malaysia (MA), were produced in Vero cell cultures. After virus propagation the infectious virus harvest is inactivated prior to purification as given in the flow chart of FIG. 1a.

[0063]1.1. Formalin Inactivation

[0064]The first inactivation step with formalin is carried out on a cell-free, infectious monovalent virus harvest, i.e. a bioreactor harvest after clarification via centrifugation. After the collection at 30 to 34.degree. C., the monovalent virus harvest is treated with about 0.9 to about 1.1 U/ml Benzonase at 30 to 34.degree. C. for 4 to 8 hours. Then it is treated with <=92 mg/l formalin for 24 to 24.5 hours at 32+/-2.degree. C.

[0065]1.2. UV Inactivation

[0066]A number of inactivation experiments with formalin-inactivated viruses are carried out using an inactivation chamber with a 65 W UV lamp and a thin layer chamber. Although full inactivation of monovalent virus harvest can be demonstrated when using flow rates of 100 liter per hour for three cycles, this setup did not allow the on-line measurement of the UV signal. The Vero cell culture medium used for Influenza production contains various organic compounds responsible for absorption of the UV signal. Therefore, the system, is equipped with a 110 W lamp allowing a continuous monitoring of the UV signal during monovalent virus harvest treatment.

[0067]Formalin treated monovalent Influenza Panama harvest is used as a model substrate for the inactivation. For continuous inactivation with thin layer UV technology a WEDECO VISA system (Germany) equipped with a VISA lamp (110 W) is used. The UV thin layer chamber is a stainless steel 1.4435 device with a 30 mm diameter quartz tube. A calibrated UV sensor allows on-line control of the UV signal. The UV thin layer chamber is operated at a flow rate of 240+/-10 liter per hour at ambient temperature. The flow rate conditions are controlled by a calibrated flowmeter. The monovalent harvest is exposed to 10 UV cycles. After each cycle 20 liter of the UV treated monovalent harvest is removed and further purified by sucrose gradient purification using continuous ultracentrifugation.

[0068]1.3. Safety Test

[0069]The standard Vero safety test is a highly stringent quality test for the residual infectivity of inactivated influenza strains. The test is also applicable to other viruses. A monovalent bulk product, i.e. purified virus antigen after sucrose gradient centrifugation and ultra-diafiltration, is added to 5 Roux flasks (4 ml/flask). After incubating for 7 days at 32.degree. C. in Vero culture medium, the cell cultures are harvested, pooled and added to 5 Roux flasks (10 ml/flask). After another incubation step for 7 days at 32.degree. C., the cell cultures are harvested, pooled, and tested for hemagglutinin (HA).

[0070]The HA-test is based on the fact that Influenza viruses can bind erythrocytes using their surface protein hemagglutinin. The test is carried out in a sterile environment. A suspension of Influenza viruses with a defined HA titer serves as a positive control and a 0.9% NaCl solution serves as a negative control. 50 .mu.l of a 1:2 dilution in 0.9% NaCl of a sample to be tested are given into one well of a 96-well plate. To each well 50 .mu.l of a solution containing chicken erythrocytes is added. Subsequently, the plates are incubated for 30 to 45 minutes at room temperature. Then the hemagglutination is visually determined, wherein, if five wells containing the same sample do not show any hemagglutination, the sample passed the HA test.

Example 2

Purification by Ultracentrifugation

[0071]During purification of influenza virus antigen, the monovalent harvest (MVH) is concentrated by centrifugation. A continuous flow centrifugation procedure can be applied for the manufacture of the Vero cell culture grown viral vaccine based on a sucrose gradient formed using an aqueous sucrose solution. The centrifuge model used was equipped with a preclarifier. Small scale experiments with a density gradient formed using approx. 42% and 55% (w/w) sucrose solution in 20 mM Tris-buffer were carried out under different centrifugation conditions. In addition, ultracentrifugation without preclarifier but with increased g-forces turned out to be a valuable tool for yield improvement.

[0072]Monovalent Influenza virus harvests (MVHs) were used for the comparative studies. The MVHs were purified with continuous ultracentrifugation with a laboratory centrifuge model RK-6 at 35.000 rpm.

Example 3

Purification/Processing

[0073]For an influenza candidate vaccine, three different strains of influenza were purified and collected from ultracentrifugation as described in example 2. Antigen yields were different in the Peak Pools. The influenza strain New Calcdonia had the lowest antigen yield followed by Hiroshima and finally Malaysia. Protein content was highest in the Malaysia and lowest in the Hiroshima. SRD (Single Radial Immunodiffusion Assay (HA-quantification)) to Total Protein ratios were comparable in Peak Pools from Malaysia and New Calcdonia, but higher in the Hiroshima (Table 1).

TABLE-US-00001 TABLE 1 Analytical results of peak pools HR05/61 MA04/61 NC99/51 Influenza strain Hiroshima Malaysia New Caledonia Amount (ml (g)) 840.4 (1000) 420.2 (500.1) 420.2 (500) SRD (.mu.g/ml) 246.2 426.6 194.9 Protein conc. 487 1495 764 (.mu.g/ml) by Bradford SRD/protein ratio 0.51 0.28 0.26 VERO Protein conc. 6.2 19.7 18.9 (.mu.g/ml) by ELISA

Further processing was according to the following overview:

[0074]3.1. Dilution of Peak Pools

[0075]The Peak Pools are diluted 3 fold with TBS buffer to reduce sucrose concentration for reduction of viscosity.

[0076]3.2. First Homogenization Peak Pool

[0077]The diluted Peak Pool is treated with a high pressure homogenizer "NS 1001L Panda" (Niro Soavi S.p.A.). The virus suspension is passed through the homogenizer 3 times with 800 bar. This pressure is sufficient to improve subsequent processing steps by disrupting virus aggregates.

[0078]3.3. Benzonase Addition

[0079]Benzonase, a recombinant nuclease produced in E. coli, is added to the virus suspension at a final concentration of 3 U/ml to degrade cell derived DNA.

[0080]3.4. Pressure Filtration

[0081]After Benzonase addition, a 0.22 .mu.m pressure filtration is performed to keep the virus suspension free of advantitious organisms such as bacteria during the subsequent incubation period. Incubation is performed at 32.degree. C. over night.

[0082]3.5. Ultra/Diafiltration

[0083]After Benzonase incubation is finished, Ultra/Diafiltration is performed with a 30 kD suspended channel ultrafiltration membrane (Pall) with a filtration area of 0.1 m.sup.2 at small scale and 0,5 m2 at pilot scale. The Ultraretentate is diafiltrated with 10 Retentate volumes of TBS (Tris buffered saline)+0.008% TritonX100 (w/w).

[0084]3.6. Triton X100 Addition for Solubilization and Incubation

[0085]For Virus splitting, TritonX100 is added to a final concentration of 0.5% (w/w) and incubated over night at room temperature.

[0086]3.7. Diafiltration II

[0087]For removal of the high Triton X100 concentration, Diafiltration is performed with a 30 kD suspended channel ultrafiltration membrane (Pall). The Ultraretentate is diafiltrated with 15 retentate volumes of TBS (Tris buffered saline).

[0088]3.8. Formaldehyde Addition and Incubation

[0089]Formalin is added into the Ultra/Diaretentate to a final concentration of 0.025% for antigen stabilization. The incubation is performed for 18-24 hours at room temperature. Formalin is a saturated aqueous solution of .about.36-37% formaldehyde gas.

[0090]3.9. Triton X100 Concentration Determination by HPLC

[0091]Subsequent processing steps consist of a dilution step and a further Ultra/Diafiltration. In order to be able to dilute the UDR below the CMC for Triton X 100 (TX 100, .about.0.015%, 250 .mu.M, in aqueous solution), an analytic TX 100 determination step was introduced to define the concentration of TX 100. The dilution factor is dependent on this TX 100 concentration.

[0092]3.10. Dilution of the UDR Below the Critical Micellar Concentration for TX 100

[0093]The Ultra/Diaretentate containing residual TX 100 of about 0.1-0.2% (determined by HPLC) is diluted with TBS to a final TX 100 concentration of 0.008%, a concentration clearly below the CMC (Critical Micellar Concentration).

[0094]3.11. Ultra/Diafiltration III

[0095]Ultra/Diafiltration is performed with the identical 30 kD suspended channel ultrafiltration membrane. The Ultraretentate is diafiltrated with 5 Retentate volumes of TBS (Tris buffered saline)+5 VC TBS+0.008% TritonX100 (w/w).

[0096]3.12. Detergent Stabilisation

[0097]After reduction of the TX 100 concentration to the target level, Tween 80 is added into the suspension to a final concentration of 0.125%.+-.0,025% for further virus antigen stabilization. This avoids antigen re-aggregation due to too low TX 100 concentrations.

[0098]3.13. Second Homogenization

[0099]A second high pressure homogenization step is carried out to keep antigen loss low at the 0.22 .mu.m filtration step. The same homogenizer as described in section 3.2 with identical settings is used.

[0100]3.14. Sterile Filtration

[0101]Following the 2nd homogenization step a sterile filtration is carried out using 0.22 .mu.m filters (Millipore). The sterile filtered Bulk material is termed Monovalent Bulk (MVB).

Example 4

Results

TABLE-US-00002 [0102]TABLE 2 Results from purification after ultracentrifugation as exemplified for a split virus (Hiroshima): Peak DIL UDR1 UDR2 pool (1:3) HOM1 PFIL 30K 30K UDR HOM2 MVB Amount g 500 1501.6 1479.8 1537.5 410.4 411.7 421.8 414.9 421.5 Optical density OD, 405 nm / 0.82 0.24 0.20 0.86 0.72 0.88 0.18 0.15 SRD (NIBSC) .mu.g/ml 194.9 58.7 56.1 52.9 130.9 110.3 84 86.5 74.6 SRD total mg 81.9 77.4 78.2 73.9 53.7 45.4 35.4 35.9 31.5 Protein .mu.g/ml 764 / / / / / / / 385 Protein total mg 382 / / / / / / / 162.3 VERO Protein .mu.g/ml 18.9 4.5 4.4 3.8 10.8 6.3 4 5 4.7 conc. by ELISA Total VERO mg 8 6.1 5.9 5.2 4.4 2.6 1.7 2.1 2 Protein by ELISA Vero DNA ng/ml / / / / / / / / 0.64 Vero DNA total .mu.g / / / / / / / / 0.27 TX100 (%) / / / / 0.482 0.101 0.018 0.017 0.017 Tween80 (%) / / / / / / / / 0.115 DIL (1:3) . . . dilution of peakpool; UDR . . . Ultradiaretentate after ultradiafiltration; HOM-1, HOM-2 . . . homogenization 1 and 2; PFIL . . . 0.22 .mu.m pressure-filtration; MVB . . . monovalent bulk

The total SRD in the MVB was 73 mg. Total Vero protein levels were reduced from 5.2 mg to 1 mg, a reduction of 80.8%. Total Vero DNA was reduced to 0.28 .mu.g in the MVB. Total protein was reduced from 487 mg to 212 mg constituting a reduction of 56.5%.

[0103]Similar results were obtained for the Malaysia strain: Total Vero protein could be reduced from 8.3 mg to 2.4 mg, which is a reduction of approximately 67.5% from the Peak Pool to the MVB. Vero DNA content in the MVB was 1.8 .mu.g. Reduction of Total Protein during purification was 58.6% from 748 mg to 310 mg.

[0104]For the New Calcdonia strain at the end of purification, total Vero protein could be reduced from 8 mg in the Peak Pool to 2 mg in the MVB, which is a reduction of 75%. Total Vero DNA content in the MVB was 0.27 .mu.g. Total protein was reduced from 382 mg in the Peak Pool to 162 mg in the MVB, which constitutes a reduction of 57.6%.

[0105]The purification process is very consistent and robust. A highly purified virus preparation resulted from the successful reduction of host cell protein and DNA as well as process chemicals like Benzonase, Sucrose, Formaldehyde and Triton X100 as well as the lack of Endotoxins. All preparations were sterile after production. SRD to protein ratios complied with specifications in all three MVBs.

4.) Baxter Completes Production of First Commercial Batches of A/H1N1

Pandemic Vaccine

Source:

http://www.baxter.com/about_baxter/press_room/press_releases/2009/08_05_09-A-H1N1.html

DEERFIELD, Ill., August 5, 2009 — Baxter International Inc. (NYSE: BAX) today announced that it completed production of its first commercial batches of CELVAPAN A/H1N1 pandemic vaccine in late July and is discussing plans for distribution with national health authorities, subject to obtaining appropriate authorizations. CELVAPAN, the brand name for the company's A/H1N1 pandemic influenza vaccine, is made using Baxter's proprietary Vero cell culture technology.
 

Baxter plans to deliver initial quantities of CELVAPAN to national public health authorities that have pandemic agreements with the company. These health authorities placed orders for the vaccine following the World Health Organization's (WHO) elevation of the pandemic alert level to phase 6 and declaration of a pandemic.
Baxter's proprietary Vero cell production technology is meeting the company's expectations to rapidly produce a vaccine in response to a pandemic. CELVAPAN was developed and commercially produced using this process within 12 weeks of receiving the A/H1N1 virus strain, which represents an innovation in vaccine production.
“We are pleased with our company's ability to meet its expected timelines in developing and producing CELVAPAN,” said Joy Amundson, corporate vice president and president of Baxter BioScience. “This is an encouraging validation of our science, our Vero cell vaccine technology and the teamwork at Baxter in meeting this important milestone to help address an urgent public health issue.”
 

Baxter is collaborating with regulatory authorities to ensure the company is in accordance with all requirements needed to support approval and use of CELVAPAN. “To make CELVAPAN A/H1N1 vaccine, we applied the same development, qualification and manufacturing processes used in gaining European Medicines Agency (EMEA) licensure of a mock-up pandemic vaccine,” said Hartmut J. Ehrlich, M.D., vice president of global research and development for Baxter BioScience. “The mock-up vaccine made with a different pandemic strain was tested in five clinical trials worldwide in more than 1,300 people. In addition, more than 3,500 people have been vaccinated during an ongoing phase III study.”
Confirmatory clinical trials to evaluate safety and immunogenicity of CELVAPAN A/H1N1 in adults, the elderly and children are scheduled to begin in August. Baxter has initiated its license application for CELVAPAN A/H1N1 based on the EMEA published guidelines for pandemic vaccine marketing authorization and will supplement its application post-approval with the appropriate safety and immunogenicity data from the confirmatory clinical trials. Once national vaccination programs are initiated, Baxter will also conduct a large-scale observational study in people receiving CELVAPAN. In all countries, decisions to administer the vaccine will be determined by local public health authorities.
 

ABOUT BAXTER'S PANDEMIC VACCINE DEVELOPMENT
Baxter received the A/H1N1 strain for testing and evaluation from the U.S. Centers for Disease Control and Prevention (a WHO Collaborating Center) in early May. The company then undertook pre-production testing and evaluation of the virus strain to assess its growth characteristics and ability to work in the company's proprietary Vero cell culture. Based on the virus' ability to grow in Vero cell culture, Baxter initiated commercial production on June 3, 2009. Bulk CELVAPAN vaccine is produced at its large-scale commercial facility in Bohumil, Czech Republic, and is sent to Vienna, Austria for the final formulation, fill and finish before distribution.
Mock-up licensure is a regulatory pathway for pandemic vaccines that was created by the European Medicines Agency (EMEA) in 2004. This pathway allows for the development, evaluation and testing of a company's vaccine production capabilities using an available influenza strain that has the potential to cause a pandemic. Once a pandemic is declared and the influenza virus strain causing the pandemic is identified, the mock-up licensure allows for fast track approval of a pandemic vaccine containing the actual pandemic strain. Other countries may choose to evaluate the company's EMEA submission and use that information as the basis for their national health authority's authorization for use of the vaccine.
 

ABOUT BAXTER INTERNATIONAL INC.
Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

This release includes forward-looking statements concerning the company's vaccines products, including with respect to potential timelines. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: continued success in advancing a new technology through full-scale production, including with respect to steps required for finishing, release, shipment, and customer acceptance; remaining regulatory approvals; governments' continuing decisions with respect to orders; and other risks identified in the company's most recent filing on Form 10-K and other Securities and Exchange Commission filings, all of which are available on the company's website. The company does not undertake to update its forward-looking statements.

5.) Baxter Gets H1N1 Marketing Approval
By Zacks Equity Research
On 3:50 pm EDT, Thursday October 8, 2009
 

Source:

http://finance.yahoo.com/news/Baxter-Gets-H1N1-Marketing-zacks-1470502489.html?x=0&.v=1

Baxter International Inc. (NYSE: BAX - News) recently received marketing authorization for CELVAPAN H1N1 vaccine, commonly known as the Swine Flu vaccine, in the European Union. The company has already delivered limited quantities of H1N1 vaccine to a few countries, such as the UK and Ireland, as part of their national vaccination programs.

Presently, Baxter is conducting two clinical trials to confirm the safety and immunogenicity of CELVAPAN H1N1. These trials encompass 400 healthy adults who are 18 years and above, besides 400 children and adolescents. The safety and immunogenicity of CELVAPAN H1N1 in these trials are conducted at dose levels of 7.5µg and 3.75µg, respectively. Baxter also plans to conduct a large-scale study of CELVAPAN in 9,000 people of different age groups including children.
Preliminary safety data in adults for 7.5µg doses of vaccine indicated that the vaccine was well tolerated in these age groups. The reactions were also similar to seasonal influenza vaccines. Two 7.5µg doses of vaccine were administered in a span of 21 days. Immunogenicity data from this study are due within days. This will indicate whether a single dose of vaccine is sufficient to induce the necessary immune response.


Another study for 3.75µg doses of vaccine will indicate whether a lower dose is sufficient to induce the necessary immune response or not.

Baxter is a leading global medical products and services company that develops, manufactures and markets products to save the lives of millions of people affected by hemophilia, kidney diseases, infectious diseases, etc.
Baxter’s life-sustaining product portfolio is a hedge against the current economic turmoil. The company’s main competitors include Becton, Dickinson and Co. (NYSE: BDX - News) and Johnson & Johnson (NYSE: JNJ - News).
 

6.) Case about Bird Flu.

Paypal donations for criminal charges against Baxter and WHO at [email protected]

Source:

http://birdflu666.wordpress.com/

« The “unseen hand” moving the chess pieces in the endgame. Just who is behind WHO?
Baxter to evaluate safety of its own H1N1 vaccines in New Zealand »

Baxter scientists who patented the H1N1 “swine flu” vaccine in August 2007 have shares in Baxter and so stand to profit directly from “recommending” H1N1 flu jab to WHO in conflict of interest
By JB

Baxter, the vaccine company found to have contaminated 72 kilos of vaccine material with live bird flu virus supplied by WHO in Austria in February 2009, so nearly triggering a pandemic, has announced an increase of 7.9 per cent in second quarter profits and is looking forward to a boost in earnings from the H1N1 flu jab, which has been mandated by WHO in response to the “swine flu” pandemic, reports WSJ and CLG.

It was Baxter executives, along with their counterparts in Novartis, GSK and Sanofi, who participated in the vaccine advisory group meeting of WHO on July 7th that recommended H1N1 vaccines for the world’s population.

These H1N1 vaccines were developed by Baxter scientists based in Austria who also have shares in Baxter, and so stand to make a direct profit from the demand created by WHO’s instructions to governments to vaccinate all their populations against the H1N1.
Aso, Baxter’s Austrian-based science team led by Otfried Kistner filed the provisional application for the H1N1 vaccine in August 2007, reports CLG, almost two years before the HIN1 virus appeared in April and which the Paris based World Organization for Animal Health reported had never been seen before.

The fact that the virus had never been seen before in animal or human strongly suggests the notion that Baxter was instrumental in biosprospecting for and bioengineering the virus in the first place.

That would explain why Baxter was in a position to file a patent in August 2007. The existence of this patent also reinforces the notion that it was Baxter that released the “swine flu” virus in April. After all, where did it this previously unseen virus come from if not from the lab of the company that patented it 2 years earlier? A Baxter facility is close to the location where the “swine flu” first mysteriously appeared in Mexico City.

The Baxter H1N1 application is filed by a team of Austrian, German staff including Otfried Kistner, Ph.D., and P. Noel Barrett, Ph.D., for the Baxter H5N1 Pandemic Influenza Vaccine Clinical Study Team, who also report they have shares in Baxter in a clincial study on that same H1N1 vaccine published in the New England Journal of Medicine.
CLG reports: “Baxter Vaccine Patent Application US 2009/0060950 A1 –’In particular preferred embodiments the composition or vaccine comprises more than one antigen…..such as influenza A and influenza B in particular selected from of one or more of the human H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, H10N7 subtypes, of the pig flu H1N1, H1N2, H3N1 and H3N2 subtypes, of the dog or horse flu H7N7, H3N8 subtypes or of the avian H5N1, H7N2, H1N7, H7N3, H13N6, H5N9, H11N6, H3N8, H9N2, H5N2, H4N8, H10N7, H2N2, H8N4, H14N5, H6N5, H12N5 subtypes.’

Also, Ehrlich, Kistner and Barret published a clinical trial in the New England Journal of Medicine ((Previous Volume 358:2573-2584 June 12, 2008 Number 24)
on the safety of an H5N1 whole-virus vaccine produced on Vero cell cultures and its ability to induce antibodies capable of neutralizing various H5N1 strains, in which they concluded that the use of adjuvants did not improve the antibody response.
http://content.nejm.org/cgi/content/short/358/24/2573

And yet Baxter and WHO recommended oil-in-water adjuvants for the H1N1 “vaccines”.
These adjuvants have been associated with many diseases.
“SAGE recommended that promoting production and use of vaccines such as those that are formulated with oil-in-water adjuvants and live attenuated influenza vaccines was important,” says the WHO pandemic briefing note of July 13th.
http://www.who.int/csr/disease/swineflu/notes/h1n1_vaccine_20090713/en/index.html

In addtion, WHO announced on July 16th that countries with “swine flu” cases no longer need to report them.
Pandemic (H1N1) 2009 briefing note 3
Changes in reporting requirements for pandemic (H1N1) 2009 virus infection
16 JULY 2009 | GENEVA — As the 2009 pandemic evolves, the data needed for risk assessment, both within affected countries and at the global level, are also changing.
At this point, further spread of the pandemic, within affected countries and to new countries, is considered inevitable.

This assumption is fully backed by experience. The 2009 influenza pandemic has spread internationally with unprecedented speed. In past pandemics, influenza viruses have needed more than six months to spread as widely as the new H1N1 virus has spread in less than six weeks.

The increasing number of cases in many countries with sustained community transmission is making it extremely difficult, if not impossible, for countries to try and confirm them through laboratory testing. Moreover, the counting of individual cases is now no longer essential in such countries for monitoring either the level or nature of the risk posed by the pandemic virus or to guide implementation of the most appropriate response measures.

And yet the same WHO calims that the “swine flu” has spread internationally with unprecedented speed. How can WHO know this if it drops the requirement for countries to suppply data on the speed and spread of that same virus? How can it track how the virus is mutating without data from countries?
In the July 13th briefing note, WHO places emphasise on collecting data for a “post-marketing surveillance” and so it is justifiable to ask why WHO does not want data for a pre marketing surveillance?

“Since new technologies are involved in the production of some pandemic vaccines, which have not yet been extensively evaluated for their safety in certain population groups, it is very important to implement post-marketing surveillance of the highest possible quality. In addition, rapid sharing of the results of immunogenicity and post-marketing safety and effectiveness studies among the international community will be essential for allowing countries to make necessary adjustments to their vaccination policies.”
 

7.) Flu Kills The Torture Memos

 by Lori Price

 Global Research, April 26, 2009

Source:

 http://www.globalresearch.ca/index.php?context=va&aid=13351

In a 'Holy convenience, Batman!' moment, a 'unique' flu virus (one likely concocted in US Army labs) overtakes media coverage of revelations that the highest levels of the US government instructed the CIA (and private contractors) to torture terror suspects.

Scientists said the virus combines genetic material from pigs, birds and humans in a way researchers have not seen before. “We are very, very concerned,” World Health Organization spokesman Thomas Abraham said. “We have what appears to be a novel virus and it has spread from human to human,” he said. “It’s all hands on deck at the moment.”

Guess where the first swine flu outbreak occurred? That's right, Fort Dix, New Jersey, in 1976. Also likely created in a US Army lab. Thirteen soldiers died, leading the US government to force a questionable vaccine on the population -- backed by a legal liability escape clause mandated by and for the pharma-terrorists. Next, people started dying not from the flu -- but from the *vaccine.*

Every major media outlet has reported the fact that US/UK bioterrorists have been manipulating the avian flu virus in university and Army labs. This new flu strain, one that 'no one has ever seen,' contains avian flu. Now, how does *that* happen?

CLG has been covering flu 'oddities' for eight years. See: Flu 'Oddities' and Flu 'Oddities' News Archives.

 ANNEX

U.S. denies producing biological weapons from bird flu samples --Media: U.S. denies Indonesia's allegation on bird flu virus 17 Mar 2008 The United States has flatly denied allegations it was producing biological weapons from bird flu samples sent by Indonesia to the World Health Organization, the English daily The Jakarta Post reported Monday. Michael H. Anderson, counselor for Public Affairs at the U.S. Embassy in Indonesia, [has issued the denial]. However, Indonesian senior biodefense researcher Isro Samihardjo said the U.S. could use bird flu virus samples from Indonesia to develop weapons at the Los Alamos Laboratory. Isro was speaking at a meeting about Health Minister Siti Fadilah Supari's newly released book here Saturday. In her book "It's Time for the World to Change, Divine Hands behind Bird Flu," Siti writes of her suspicions about a conspiracy between the U.S. and the WHO.

Experts identify genes for bird flu replication 09 Jul 2008 Scientists have identified around 100 genes that the H5N1 bird flu virus needs in a host in order to replicate, and this finding may help in the hunt for ways to block foment its proliferation.

Army: 3 vials of virus samples missing from Maryland facility 22 Apr 2009 Missing vials of a potentially dangerous virus have prompted an Army investigation into the disappearance from a lab in Maryland. The Army's Criminal Investigation Command agents have been visiting Fort Detrick in Frederick, Maryland, to investigate the disappearance of the vials. The vials contained samples of Venezuelan Equine Encephalitis... In 97 percent of cases, humans with the virus suffer flu-like symptoms, but it can be deadly in about 1 out of 100 cases, according to Caree Vander Linden, a spokeswoman for the U.S. Army Medical Research Institute of Infectious Diseases.

Scientists isolate genes that made 1918 flu lethal 29 Dec 2008 By mixing and matching a contemporary flu virus with the "Spanish flu" -- a virus that killed between 20 and 50 million people 90 years ago in history's most devastating outbreak of infectious disease -- researchers have identified a set of three genes that helped underpin the extraordinary virulence of the 1918 virus. Writing today (Dec. 29) in the Proceedings of the National Academy of Sciences, a team led by University of Wisconsin-Madison virologists Yoshihiro Kawaoka and Tokiko Watanabe identifies genes that gave the 1918 virus the capacity to reproduce in lung tissue, a hallmark of the pathogen that claimed more lives than all the battles of World War I combined.

Killer flu recreated in the lab 07 Oct 2004 Scientists have shown that tiny changes to modern flu viruses could render them as deadly as the 1918 strain which killed millions. A US team added two genes from a sample of the 1918 virus to a modern strain known to have no effect on mice. Animals exposed to this composite were dying within days of symptoms similar to those found in human victims of the 1918 pandemic.

Venture capital firm set to reap rewards on swine flu 24 Apr 2009 The swine flu outbreak is likely to benefit one of the most prolific and successful venture capital firms in the United States: Kleiner Perkins Caufield & Byers, Thomson Reuters Private Equity Week reported on Friday. Shares of the two public companies in the firm's portfolio of eight Pandemic and Bio Defense companies -- BioCryst Pharmaceuticals and Novavax -- jumped Friday on news that the swine flu killed a reported 60 people in Mexico and has infected people in the United States. The World Health Organization said the [unique] virus appears to be susceptible to Roche's flu drug Tamiflu, also known as oseltamivir, but not to older flu drugs such as amantadine.

Rumsfeld's growing stake in Tamiflu --Defense Secretary, ex-chairman of flu treatment rights holder, sees portfolio value growing. 31 Oct 2005 The prospect of a bird flu outbreak may be panicking people around the globe, but it's proving to be very good news for Defense Secretary Donald Rumsfeld and other politically connected investors in Gilead Sciences, the California biotech company that owns the rights to Tamiflu, the influenza remedy that's now the most-sought after drug in the world. Rumsfeld served as Gilead (Research)'s chairman from 1997 until he joined the Bush administration in 2001, and he still holds a Gilead stake valued at between $5 million and $25 million, according to federal financial disclosures filed by Rumsfeld.

CLG: Baxter working on vaccine to stop swine flu, though admitted sending live pandemic flu viruses to subcontractor By Lori Price 26 Apr 2009 The OMFG moment of the century. Illinois-based Baxter working on vaccine to 'stop' swine flu outbreak in Mexico 25 Apr 2009. But, looky here! Baxter admits sending live avian flu viruses to subcontractor --People familiar with biosecurity rules are dismayed by evidence that human H3N2 and avian H5N1 viruses somehow co-mingled [!] in the Orth-Donau facility. 27 Feb 2009 Is Baxter International taking a page from the Blackwater playbook? Just as Blackwater/Xe keep on killing to justify their multi-billion dollar contracts to provide 'security' in Iraq and Afghanistan, Baxter International is poised to make *billions* to vaccinate people against their pandemic.

Briton quarantined as killer flu spreads 26 Apr 2009 A British Airways cabin crew member was taken to hospital with flu-like symptoms yesterday afternoon after falling ill on a flight from Mexico City to Heathrow. The Health Protection Agency said it was keeping a close eye on the situation.

New Zealand quarantines 25 amid swine flu alert 26 Apr 2009 Twenty-five students and teachers in New Zealand, some with flu-like symptoms, were quarantined and tested for swine flu after returning from a trip to Mexico, officials said Sunday, as Asia stepped up surveillance for the deadly virus.

Minister: 10 NZ students likely have swine flu 26 Apr 2009 New Zealand said Sunday that 10 students "likely" have swine flu after a school trip to Mexico, as governments across Asia began quarantining those with symptoms of the deadly virus and some issued travel warnings for Mexico.

Mexico Takes Powers to Isolate Cases of Swine Flu --The Centers for Disease Control and Prevention in Atlanta said Saturday that it had sent a team of experts to Mexico to assist with the investigation cover-up of the outbreak.26 Apr 2009 This sprawling capital was on edge Saturday as... President [sic] Felipe Calderón published an order that would give his government emergency powers to address a deadly flu outbreak, including isolating those who have contracted the virus, inspecting the homes of affected people and ordering the cancellation of public events. The newspaper Reforma reported that President Obama, who recently visited Mexico, was escorted around Mexico City’s national anthropology museum on April 16 by Felipe Solis, an archaeologist who died the next day from flu-like symptoms.

Mexico declares national emergency amid outbreak 25 Apr 2009 President [sic] Felipe Calderon declared a national emergency Saturday, authorizing federal officials to quarantine the sick, shut down public events and businesses, and take other measures to contain the virus’ spread. Many in this crowded capital of 20 million are holing up or fleeing town as Mexico braces for what the World Health Organization warns could explode into a deadly global flu epidemic.

Mexico May Isolate Patients With Deadly Swine Flu Strain --The decree published Saturday says Mr. Calderón has the authority to invoke the new powers whenever the situation warrants. 26 Apr 2009 President [Bush troll] Felipe Calderón published an order Saturday that would give his government extraordinary powers to address a deadly flu epidemic, including isolating those affected by the rare virus, inspecting their homes and ordering the closure of any public events that might result in more infection... Because of the situation, the World Health Organization planned to consider raising the world pandemic flu alert to 4 from 3. Such a high level of alert -- meaning that sustained human-to-human transmission of a new virus has been detected -- has not been reached in recent years, even with the H5N1 avian flu circulating in Asia and Egypt...

Pandemic fear as killer flu spreads 26 Apr 2009 A deadly strain of flu that combines elements of swine, avian and human viruses could spread around the world after emerging simultaneously in Mexico and the United States, experts warned yesterday. Margaret Chan, director-general of the World Health Organisation, said the disease had "pandemic potential"... Up to 68 people have died from pneumonia caused by a flu-like illness in Mexico, where 1,004 suspected cases have been reported. Tests have so far confirmed that 20 of the deaths were caused by a hitherto unknown swine flu.

Texas Gov orders 37,430 courses of antiviral medications from Strategic National Stockpile --New possible case of swine flu identified in Texas 25 Apr 2009 A Texas high school where two students are confirmed to have swine flu is temporarily closing after a new possible case of swine flu was identified there, state health officials announced Saturday. Carrie Williams, a state Department of Health Services spokeswoman in Austin, confirmed Saturday that another student in Guadalupe County near San Antonio is now believed to have the illness... Gov. Rick Perry announced Saturday that because of the outbreak he was asking the Centers for Disease Control and Prevention to give Texas 37,430 courses of antiviral medications from the Strategic National Stockpile to prevent the spread of swine flu.

11 more suspected swine flu cases in U.S. --Total reaches 19 26 Apr 2009 Kansas health authorities had confirmed two new cases of swine flu in their state, California has confirmed another case in Imperial County and New York City officials have identified eight probable cases, bringing the U.S. total to 19 likely cases. The Centers for Disease Control and Prevention had previously identified six cases in San Diego and Imperial counties and two cases in Guadalupe County, Texas.

Officials: 8 NYC Students Probably Have Swine Flu --Department of Health Officials Tests 75 Students at St. Francis Preparatory School in Queens 25 Apr 2009 At least eight students at a high school in New York City probably have human swine influenza, but authorities don't know for sure whether they have the strain that has killed people in Mexico. City health officials say more than 100 students at the private St. Francis Preparatory School in Queens have come down with a fever, sore throat and other aches and pains.

Two swine flu cases confirmed in Dickinson County 25 Apr 2009 The Kansas Department of Health and Environment has confirmed two cases of swine flu involving a husband and wife in Dickinson County. KDHE officials said one had recovered and the other is still being treated, but neither was hospitalized. One of the patients had recently traveled to Mexico, flying in and out of Wichita, the KDHE said.

Deadly new flu strain erupts in Mexico, U.S. 24 Apr 2009 A strain of flu never seen before has killed up to 60 people in Mexico and also appeared in the United States, where eight people were infected but recovered, health officials said on Friday. Mexico's government said at least 20 people have died of the flu and it may also be responsible for 40 other deaths. The WHO said the virus appears to be susceptible to Roche AG's flu drug Tamiflu, also known as oseltamivir, but not to older flu drugs such as amantadine. [Lucky Rumsfeld!]

Swine Flu May Be Named Event of International Concern 25 Apr 2009 The World Health Organization is set to declare the deadly swine flu virus outbreak in Mexico and the U.S. a global concern, potentially prompting travel advisories, said a person familiar with the matter. An emergency committee of the WHO in Geneva will declare the outbreak "a public health event of international concern" in a teleconference that began at 4 p.m. today, said the person, who spoke on condition of anonymity because the meeting is confidential.

Outbreak in Mexico, U.S. tied to new swine flu --Source of unique virus a mystery; CDC expects more cases 24 Apr 2009 The unique strain of swine flu found in seven people in California and Texas has been connected to the deadly flu that has broken out in Mexico, killing as many as 61 people. The strain has never been seen before and is raising fears of a possible pandemic across North America. The World Health Organization said the virus that killed at least 12 of the victims in Mexico had the same genetic structure as an outbreak discovered in California. [See: Flu 'Oddities'.]

Navy Experimenting With Flu at Mexican Border --Mexico Shuts Schools Amid Deadly Flu Outbreak 25 Apr 2009 Mexican officials, scrambling to control a swine flu outbreak that has killed at least 16 people and possibly dozens more in recent weeks... The unusual strain this year was noticed, said Dr. Anne Schuchat, director of respiratory diseases the Centers for Disease Control and Prevention, only because the agency was trying out a new diagnostic test at a Navy laboratory and doing more testing than usual through a new Border Infectious Disease Surveillance Project along the Mexican border. [See: The U.S.-Mexico Border Infectious Disease Surveillance Project: Establishing Bi-national Border Surveillance (cdc.gov)]

Possible Swine Flu Outbreak At NYC Prep School --Department of Health Officials Testing 75 Students At St. Francis Preparatory School In Queens 24 Apr 2009 New York City health officials say that about 75 students at a Queens high school have fallen ill with flu-like symptoms and testing is under way to rule out the strain of swine flu that has killed dozens in Mexico. The Health Department's Dr. Don Weiss said Friday that a team of agency doctors and investigators were dispatched to the private St. Francis Preparatory School the previous day after students reported fever, sore throat, cough, aches and pains.

Mexico flu deaths raise fears of global epidemic --Unique virus connected to cases in Calif. and Texas; source still a mystery 24 Apr 2009 Mexico shut down schools, museums, libraries and state-run theaters across its overcrowded capital Friday in hopes of containing a swine flu outbreak that authorities say killed at least 20 people -- and perhaps dozens more. World health authorities worried openly that the strange new virus could become a global epidemic. The U.S. Centers for Disease Control and Prevention said tests show some of the Mexico victims died from the same new strain of swine flu that sickened eight people in Texas and California. Of the 14 samples tested from Mexico, seven were matches, said the CDC's acting director Dr. Richard Besser.

'Laboratory testing showed that the virus does not match any known flu strains.' In California and Texas, 5 New Swine Flu Cases 24 Apr 2009 Government scientists have identified five more people who have been infected with swine flu, apparently confirming suspicions that the unusual strain of the respiratory infection is spreading from person to person, federal health officials said yesterday. Three new cases were found in California and two in Texas, bringing the total number of confirmed cases to seven, officials at the federal Centers for Disease Control and Prevention in Atlanta said... Genetic analysis of the virus indicates it is highly unusual: It is a hybrid that resulted from a [Fort Detrick?] combination of four different viruses.'

Troops Could Be Sent to Border --Under $350M plan, National Guard would be aimed at drug war 24 Apr 2009 The Pentagon and Homeland Security Department are developing contingency plans to send National Guard troops to the U.S.-Mexican border under a $350 million initiative that would expand the U.S. military's role in [fomenting] the drug war, according to Obama administration officials.

In 2002, Military Agency Warned Against 'Torture' --Extreme Duress Could Yield Unreliable Information, It Said 24 Apr 2009 The military agency that provided advice on harsh interrogation techniques for use against terrorism suspects referred to the application of extreme duress as "torture" in a July 2002 document sent to the Pentagon's chief lawyer and warned that it would produce "unreliable information." "The unintended consequence of a U.S. policy that provides for the torture of prisoners is that it could be used by our adversaries as justification for the torture of captured U.S. personnel," says the document, an unsigned two-page attachment to a memo by the military's Joint Personnel Recovery Agency. Parts of the attachment, obtained in full by The Washington Post, were quoted in a Senate report on harsh interrogation released this week. [Oops! Looks like the PentaPost will have to stop calling torture 'enhanced interrogation techniques' because the Pentagon itself calls torture torture. --LRP]

Memo From the Joint Personnel Recovery Agency 24 Apr 2009

Cheney Requests Release of 2 CIA Reports on Interrogations 25 Apr 2009 Former vice president [sic] Richard B. Cheney is asking for the release of two CIA reports in his bid to marshal evidence that coercive interrogation tactics such as waterboarding helped thwart terrorist plots, according to documents released yesterday by the National Archives and Records Administration.

UK High Court demands U.S. torture documents 22 Apr 2009 The chief justice of the British High Court on Wednesday gave the British government one week to obtain the U.S. release of classified information about the alleged torture of a British resident [Binyam Mohamed] who'd been detained at the U.S. military prison in Guantanamo Bay, Cuba. The court indicated that it would issue its own order if the government doesn't respond or justify why continued secrecy is warranted.

DoD to carry out 'military missions' during pandemic, WMD attack

DoD to 'augment civilian law' during pandemic or bioterror attack

Global Research Articles by Lori Price

8.) Stop Baxter International

Source:

http://www.thepetitionsite.com/1/stop-baxter-international-from-developing-the-h1n1-vaccine

This petition is no longer about stopping Baxter from making the H1N1 vaccine as it s too late, but it is now about getting enough signatures to have them investigated and hopefully shut down.

Baxter International is a drug company that has been at the center of three major drug contamination scandals, one of them occurred only a few months ago in February of this year:

1. Live avian flu was found in flu vaccines intended for human use:
http://www.torontosun.com/news/canada/2009/02/27/8560781.html

2. They sent out Heparin that did not even contain the main ingredient, but instead contained a chemically similar compound:
http://www.nowpublic.com/health/heparin-blood-thinner-baxter-partially-contaminated-fda-announced

3. And in the 1980's the FDA banned Baxter from using certain blood products known to contain HIV and AIDS. So what did they do? They sold them to foreign countries with no warning about what they contained:
http://www.businessweek.com/archives/1996/b3466083.arc.htm

Two instances is a trend, but three is a pattern. All of these contaminations were carried out with prior knowledge and were therefore malicious acts.

Still, the WHO selected Baxter to create the H1N1 vaccine just two months after live avian flu was found in vaccines intended for human use. As well, it has been revealed that due to the fact it was made in a Biohazard safety level 3 facility, these two substances, a live deadly virus and a flu vaccine, could never come into contact accidentally.

As a country, as a global community, we cannot allow this to continue. Baxter is not capable of safely manufacturing products for human use and should not be allowed to do so. Please sign this petition, and pass it on to everyone you know and love, so we can keep ourselves safe from harm.

I was recently contacted by the someone from this petition site saying a reported called them wanting to interview me about this petition. I bought it and phoned and left my full name and number and they never called back. I looked up the name of the person I called and it turned her name was no where on the site of the company she said she worked for. Baxter has my info and that is scary.

As well, I am not longer allowed to share this petition on Facebook because 'someone' reported it as abusive and it is now banned. I need your help. It is scary out here.

Thank you for your time.

9.) Periodista denuncia a Baxter Laboratorios ante el FBI: La H1N1 es una Conspiracion.

Fuente: Youtube.com

9.) Journalist denounces Baxter Laboratories at the FBI: The H1N1 is a Conspiracy

Source: youtube.com

       The six parts of the interview/ las 6 partes de la entrevista

http://www.youtube.com/watch?v=DiELv7lmtT0&feature=player_embedded#

http://www.youtube.com/watch?v=kf8AzCrR-RE&NR=1

http://www.youtube.com/watch?v=H1rimu2r92o

http://www.youtube.com/watch?v=4VX6kmDHugc

http://www.youtube.com/watch?v=rG99RmVSsQ8

http://www.youtube.com/watch?v=xzMDynUF4p4

                                        
                                                Jane burgmeister

                                            [email protected]

10.) Virginia Teen Suffers Severe Adverse Effects After Getting H1N1 & Seasonal Flu Shots

 11 november 2009

Source:

http://www.wusa9.com/news/local/story.aspx?storyid=93619&catid=168

ALEXANDRIA, Va. (WUSA) --- An active and healthy 14-year-old can barely walk after taking the H1N1 and seasonal flu vaccines.

Jordan McFarland has been diagnosed with a rare disease that is triggered by the flu shots. It's called Guillain Barre Syndrome, an extremely rare disorder that causes a patient's immune system to attack the nerves.

McFarland came down with symptoms within 24 hours of taking the two vaccinations.

"I got cold really quickly," he said one day after being released from the hospital. "I got a headache and I got dizzy. Slowly, these things progressed until the end of the day when I started having back spasms and I couldn't walk."

McFarland was admitted at Inova Fairfax Hospital in Falls Church, where he was diagnosed with GBS. Doctors were able to stop the most serious adverse effects but the teen still faces a long, painful and tiring recovery. He's been told it could take 6-8 weeks of physical therapy before he's fully recovered.

"It's been quite traumatic to watch your son not have the ability to control himself," said his dad, Calvin McFarland. "I had a hard time watching him move around spastically, knowing he was in so much pain and not being able to do anything about it."

"In a sense, as a parent you do carry a little sense of guilt because your kids trust you," he continued. "Kids trust their parents. Parents trust your doctors."

Doctors cannot tell family members whether Jordan's GBS was caused by the timing of both vaccinations, which were within 24 hours of each other or by the H1N1 vaccine. Jordan and his 6-year-old brother Lleyton received the shots last week.

Only six cases of GBS following the H1N1 vaccine have been reported to the Center for Disease Control. Compared to the roughly 40 million people who received shots, experts say the risk is not nearly as scary as contracting the H1N1 virus.

Even still, the McFarlands want other parents to at least be aware of the possibility.

"The same effects have occurred behind the regular flu shots as well," said the 38-year-old father. "It makes me nervous. You feel like you're playing Russian Roulette. Just roll the dice and see what happens."

11.) Riesgo de complicaciones graves relacionadas con influenza supera ampliamente el riesgo de las vacunas inyectables en mujeres embarazadas

31 Octubre 2009

Fuente:
 

http://articulos.sld.cu/influenzaporcina/2009/10/31/riesgo-de-complicaciones-graves-relacionadas-con-influenza-supera-ampliamente-el-riesgo-de-las-vacunas-inyectables-en-mujeres-embarazadas/

Las mujeres embarazadas que contraen la influenza corren un grave riesgo por las complicaciones relacionadas con la ella, incluida la muerte, y este riesgo es mucho mayor que el riesgo de posibles efectos secundarios de las vacunas inyectables que contengan virus muertos, según arrojó una amplia revisión de información e investigaciones publicadas sobre previas influencias estacionales.
La revisión, una colaboración entre científicos del Johns Hopkins Children’s Center, la Universidad de Emory y del Hospital Infantil de Cincinnati, y publicada el 22 de octubre en la edición en línea del American Journal of Obstetrics & Gynecology, encontró evidencia sustancial y persistente de alto riesgo de complicaciones para las mujeres embarazadas — tanto en las sanas como en aquellas con condiciones médicas subyacentes - infectadas con el virus de la influenza, además de confirmar la seguridad de la vacuna. Los hallazgos, dicen los investigadores, solidifican las recomendaciones de los CDC que hacen que las mujeres embarazadas sean el grupo de mayor prioridad para recibir tanto las vacunas de la influenza H1N1 y la estacional.
“Las lecciones aprendidas de los brotes de influenza en el pasado lejano y no muy lejano son claras y también lo son los mensajes”, dice el investigador principal Pranita Tamma, MD, especialista en enfermedades infecciosas del Johns Hopkins Children’s Center. “Si usted es una mujer embarazada, vacúnese. Si usted es médico obstetra, inste a sus pacientes a vacunarse.”

http://www.medicalnewstoday.com/articles/169242.php

Because even healthy pregnant women end up in the hospital with preventable flu complications — some devastating and some fatal — at a rate far higher than that of other adults, and because of the proven effectiveness and overall safety record of flu vaccines, all pregnant women should consider getting vaccinated to prevent complications in both the expectant mother and her offspring, researchers say.
“Healthcare providers will play a key role in women’s decisions about whether or not to be vaccinated against H1N1,” says study senior investigator Saad Omer, M.B.B.S., M.P.H. Ph.D., of Emory University. “There is substantial evidence that vaccination is not only safe for pregnant women but that it is critical for protecting women and their infants against serious complications from the flu. Physicians and other providers should talk about risks and benefits with their patients and help alleviate any unfounded fears.”
Even though there are still no published data on the safety of the new H1N1 vaccine, experts believe it to be just as safe as the seasonal flu vaccine, Johns Hopkins’ Tamma says, because “the H1N1 vaccine is manufactured in the same rigorous way as the seasonal flu vaccines and we expect it to have a very similar safety profile as the other flu vaccines.”
In their extensive review of data from three past flu pandemics and 11 published research studies on vaccine safety outcomes over 44 years, the researchers found no increased risk of either maternal complications or bad fetal results from the inactivated (injection) flu vaccine.
Researchers point out that even though study after study has found no link between the vaccine stabilizer thimerosal and autism, thimerosal-free injectable versions of the flu vaccine are available for those who have lingering concerns.
In their review, researchers say four studies have found evidence that antibodies protective against the flu, developed by the mother after vaccination, cross the placenta and transfer some protection to the fetus that lasts up to six months after birth.
Because pregnancy causes a variety of changes in the body, most notably decreased lung capacity, along with increased cardiac output and oxygen consumption, it puts pregnant women at high risk for complications. In addition, parts of the mother’s immune system are selectively suppressed, a process that offers essential protection to the fetus, but decreases the mother’s ability to fight off infection.
Other findings in the review:
– In the first four months of the H1N1 flu outbreak this spring, pregnant women were hospitalized at four times the rate of other healthy adults infected with the virus, according to the CDC.
– Pregnant women made up 13 percent of all H1N1 deaths during that period, and most of the women who died were previously healthy.
– Pregnant women do not get infected with the flu more often than other adults, but they develop more serious complications and more often. Pregnant women with underlying conditions such as asthma or diabetes are at even higher risk for complications.
– During the 1918 Spanish flu pandemic, of the 1,350 flu-infected pregnant women who were studied, half developed pneumonia, and more than half of those who did so died, with most deaths occurring during the third trimester.
– During the 1957 pandemic, nearly half of all women of childbearing age who died of the flu were pregnant.
– Eleven clinical studies closely followed pregnant women and/or their fetuses after vaccination and found no evidence of harmful side effects in either the mother or the fetus.
– The Vaccine Adverse Event Reporting System database, a national repository of self-reports of adverse vaccine effects, showed 26 reports of adverse effects between 2000 and 2003, a period during which 2 million pregnant women were vaccinated against the flu. Of the 26 reports, six had to do with wrongly administered vaccine without any negative consequences; nine reports described brief injection site tenderness; eight involved systemic symptoms, such as malaise and fever; and three were miscarriages. Investigators point out that these are self-reported events and do not establish any evidence of cause and effect either with respect to either miscarriage or side effects.
The research was funded partially by an NIH fellowship training grant to Pranita Tamma. Co-investigator Neal Halsey, M.D., of Johns Hopkins, receives grant support from NIH, CDC, Berna, Intercel, Merck and Novartis, none of which went toward this particular research.
Other investigators in the study include Kevin Ault, M.D., and Carlos Del Rio, M.D., of Emory University; and Mark Steinhoff, M.D., of Cincinnati Children’s Hospital.
Source: Johns Hopkins Medicine

 

12.)THIMEROSAL, AUTISM AND VACCINES..../TIMEROSAL, AUTISMO Y VACUNAS.

Source:

Dr. Jose Lapenta Dermatologist /THE DERMAGIC EXPRESS mailing list

13.)Adverse reactions to H1N1 vaccine few, far between

 Benefit of shot outweighs risk, experts suggest

 By Pauline Tam, The Ottawa CitizenNovember 11, 2009

 http://www.ottawacitizen.com/health/Adverse+reactions+H1N1+vaccine+between/2209017/story.html

 Public-health officials in Ottawa have received 19 confirmed reports of allergic reactions to the H1N1 flu shot since the city's vaccination campaign began more than two weeks ago.

Of that number, seven people were transferred to hospital emergency rooms, but to date, none has required hospitalization, said Dr. Nadine Sicard, Ottawa's associate medical officer of health.

Another 11 cases are being investigated by health officals to determine whether they were, indeed, adverse reactions. In addition, one person was hospitalized for a reaction that was "temporarily associated, although not directly related to the vaccine," Sicard said in an e-mail. She did not provide further details.

To date, 140,000 residents, mostly those at high risk of developing complications from swine flu, have received the pandemic vaccine. That suggests 0.01 per cent, or one in 10,000 people who were vaccinated, have so far had a suspected allergic reaction to the shot.

"This is within the expected range for a vaccine," said Sicard. Adverse reactions can range from a sore arm, which is common and does not require medical treatment, to dizziness or fainting. Serious adverse reactions that require immediate medical attention include an anaphylactic response, in which the throat closes, blood pressure plunges and airways tighten.

The maker of the H1N1 vaccine, GlaxoSmithKline, warns that up to one in 1,000 doses may result in an allergic reaction leading to a "dangerous decrease of blood pressure."

Sicard said early data suggests about one in 1,000 Ottawa residents who have received the shot have reported some reaction within 15 minutes of getting it. "These are mostly hives and tingling on the tongue that we would regard as significant and reportable," said Sicard. "Some have been fainting episodes and a handful have been clinical allergic reactions requiring treatment."

14.) Seasonal Flu, H1N1 Medications – Side Effects, Adverse Reactions & Cautions

Source:

http://www.wellsphere.com/health-education-article/seasonal-flu-h1n1-medications-side-effects-adverse-reactions-cautions/828778

Posted Oct 07 2009 2:57pm

 

15.) Lancet recommends caution for H1N1 vaccinations; ajduvants merit concern http://www.generationrescue.org/binstock/090809-Lancet-caution-H1N1-vaccination.htm

Teresa Binstock Researcher in Developmental & Behavioral Neuroanatomy August 09, 2009 Once again, a specter of flu haunts the media. Messages are conflicted. News media repeatedly mention that the H1N1 flu is generally mild, even as we are told to fear the H1N1 swine flu. Irony abounds. Often, flu vaccines in prior flu seasons have been found to be ineffective because that season's vaccine strain was not identical to the wild-type strain that became widespread, yet recent media reports tell us that an H1N1 vaccine will be effective even if H1N1 mutates into a different strain. The Lancet - a peer-reviewed medical journal - recently editorialized on behalf of caution in regard to fast-tracking mass vaccinations (1). After free registration, the essay can be viewed online. Oddly, The Lancet editorial mentions vaccine adjuvants but does not dwell upon their documented side-effects. Indeed, several vaccine ingredients merit concern, including mercury, aluminum, live viruses, and squalene. For instance, despite assurances that thimerosal injections do no harm, an increasing body of peer-reviewed evidence describes adverse effects of vaccinal thimerosal (eg, 2). Aluminum is associated with neurodegeneration (eg, 3), and the adjuvant squalene is associated with arthritic pathologies and with Gulf War Syndrome (4-6). Questions need be answered. Why is there a mass vaccination program with vaccines untested for safety when H1N1 swine flu cases are generally mild? Why a massive anti-H1N1 vaccination program when the rapidly developed H1N1 vaccine may not be effective against a mutated strain, when various H1N1 vaccine ingredients have a record of toxicity and adverse effects? I am saddened by a possibility: Is the creating of chronic pathologies by means of vaccination an unstated intention of pharmaceutical companies and their eager servants in the FDA and CDC? Alternatively, has vaccinology become dominated by True Believers who shun findings of adverse effects? Conclusion & recommendation: This brief essay calls attention to ironies in the so-called "H1N1 pandemic" and amid hoopla urging mass vaccination without real testing for safety.  Via several online essays (4-5) and a well written, thoroughly citationed book (4b), individuals who may be subjected to untested vaccines are encouraged to read more about squalene and other adjuvants which hyper-stimulate immunity and have a track record of adverse effects. References: 1. Supply and safety issues surrounding an H1N1 vaccine Lancet. 2009 Aug 1;374(9687):358. http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673609613957.pdf 2. Hepatitis B triple series vaccine and developmental disability in US children aged 1-9 years Carolyn Gallagher ; Melody Goodman Stony Brook University Medical Center Toxicol Environ Chem 2008 90(5):997-1008. {free online} http://fourteenstudies.org/pdf/hep_b.pd This study investigated the association between vaccination with the Hepatitis B triple series vaccine prior to 2000 and developmental disability in children aged 1-9 years (n = 1824), proxied by parental report that their child receives early intervention or special education services (EIS). National Health and Nutrition Examination Survey 1999-2000 data were analyzed and adjusted for survey design by Taylor Linearization using SAS version 9.1 software, with SAS callable SUDAAN version 9.0.1. The odds of receiving EIS were approximately nine times as great for vaccinated boys (n = 46) as for unvaccinated boys (n = 7), after adjustment for confounders. This study found statistically significant evidence to suggest that boys in United States who were vaccinated with the triple series Hepatitis B vaccine, during the time period in which vaccines were manufactured with thimerosal, were more susceptible to developmental disability than were unvaccinated boys. 3.  Effects of aluminum on the nervous system and its possible link with neurodegenerative diseases Kawahara M. J Alzheimers Dis. 2005 Nov;8(2):171-82. Aluminum is environmentally abundant, but not an essential element. Aluminum has been associated with several neurodegenerative diseases, such as dialysis encephalopathy, amyotrophic lateral sclerosis and Parkinsonism dementia in the Kii peninsula and Guam, and in particular, Alzheimer's disease. Although this association remains controversial, there is increasing evidence which suggests the implication of metal homeostasis in the pathogenesis of Alzheimer's disease. Aluminum, zinc, copper, and iron cause the conformational changes of Alzheimer's amyloid-beta protein. Al causes the accumulation of tau protein and amyloid-beta protein in experimental animals. Aluminum induces neuronal apoptosis in vivo as well as in vitro. Furthermore, a relationship between aluminum and the iron-homeostasis or calcium-homeostasis has been suggested. Based on these findings, the characteristics of aluminum neurotoxicity are reviewed, and the potential link between aluminum and neurodegenerative diseases is reconsidered. 4. Excellent source materials: 4a. Squalene: The Swine Flu Vaccine’s Dirty Little Secret Exposed by Joseph Mercola, D.O. http://tinyurl.com/lh57v8 4b. Extensive documentation about squalene's adverse effects in: Vaccine A: The Covert Government Experiment That's Killing Our Soldiers--And Why GI's Are Only The First Victims Gary Matsumoto; 2004, Basic Books. Bookfinder for used copies of Vaccine A: http://tinyurl.com/m46n33 Amazon: http://www.amazon.com/Vaccine-Government-Experiment-Killing-Soldiers/dp/046504400X B&N http://search.barnesandnoble.com/Vaccine-A/Gary-Matsumoto/e/9780465044009 5a. Adverse effects of adjuvants in vacines by Viera Scheibner, Ph.D. http://www.whale.to/vaccine/adjuvants.html 5b. Adjuvant Index http://www.vaclib.org/basic/adjuvants.htm

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DATA-MEDICOS/DERMAGIC-EXPRESS No 10-(X-18)  10/11/2.009 DR. JOSE LAPENTA R. 
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