Immunization against Viral Disease

1.         Vaccination against Viral disease

a.         Prevention of infection by the use of infections is important as there are few drugs which are useful or effective against viral infections.

b.         Prevention of viral diseases can be achieved by:

i.          the use of vaccines that induce active immunity.

ii.          administration of preformed antibody that provides passive immunity.

c.         Most viral vaccines are usually given before a known exposure; i.e., they are administered ‘preexposure’.

d.         However, the vaccines against rabies and hepatitis B, that are also effective when given ‘postexposure’, because the incubation period of these diseases is long enough that the vaccine-induced immunity can prevent the disease.

e.         Thus, the rabies vaccine is most often used in people after they have received a bite from a potentially rabid animal and the hepatitis B vaccine is used in people who have sustained a needle-stick injury.

2.         Active Immunity

a.         There are two types of vaccines that induce active immunity:

i.          those that contain live virus whose pathogenicity has been attentuated.

ii.          those that contain killed virus.

b.         Live-virus vaccines:

i.          the most successful viral vaccines are live avirulant mutants.

ii.          they have been instrumental in dramatically reducing the incidence of several important diseases of childhood and for eradicating smallpox.

iii.         the key to their success is the fact that the live virus multiplies in the recipient, eliciting a lasting immune response but causing little or no disease.

c.         Attenuated Live-virus vaccines:

i.          an attenuated virus is one that is unable to cause disease but retains its antigenicity and can induce protection.

ii.          most of the live-virus vaccines in common usage today have been derived empirically by serial passage in cultured cells.

iii.         adaptation of virus to more vigorous growth in cultured cells is fortuitously accompanied by progressive loss of virulence for the natural host.

d.         Cold-adapted mutants:

i.          derived by adaptation of virus to grow at suboptimal temperatures.

ii.          such a mutant might provide a safer vaccine for intranasal administration, in that it would replicate well at the lower temperature of the nose but not at the temperature of the more vulnerable lung

ii.          cold-adapted influenza vaccines containing mutations in its genes do not revert to virulence.

e.         Live bacteria as expression vectors:

i.          recombinant DNA technology has allowed the expression of a viral epitope on the surface of a bacterium.

ii.          the general approach is to insert the DNA encoding a protective viral epitope into a region of the genome of a bacterium that encodes a prominent surface domain on a protein normally situated on the organism’s exterior.

iii.         enteric bacteria which multiply naturally in the gut seem to be ideal expression vectors for presenting protective epitopes of virulent enteric viruses to the gut-associated lymphoid tissue.

iv.         the main candidates currently under development as potential vehicles are attenuated strains of Salmonella typhi, Escherichia coli, and BCG, the world’s most widely used live bacterial vaccine.

f.          Use of Live-virus vaccines:

3.         Inactivated Virus

a.         Inactivated virus vaccines:

i.          inactivated vaccines are made from virulent virus by chemically destroying its infectivity while retaining its immunogenicity.

ii.          the traditional inactivating agent was formaldehyde, but this is being supplanted by b-propiolactone and ethylenimines.

iii.         being noninfectious, such vaccines are generally safe but need to be injected in large amounts to elicit an antibody response commensurate with that attainable by a much smaller dose of live-virus vaccine.

iv.         normally, even the primary course comprises two or three injections, and further booster doses may be required at intervals over the succeeding years to revive waning immunity.

b.         Purified Protein vaccines:

i.          involves removal of all nonessential components of the virion and inoculate only the relevant immunogen, namely, the particular surface protein against which neutralizing antibodies are directed.

ii.          example: the HA and NA glycoproteins can be extracted from influenza virions with detergent and used as a subunit vaccine.

c.         Use of killed viral vaccines:

4.         Characteristics of live and kill viral vaccines

5.         Current viral vaccines

6.         Synthetic Vaccines

a.         Techniques have been developed for locating and defining epitopes on viral proteins, and it is possible to synthesize peptides corresponding to these antigenic domains.

b.         However, the results are disappointing in practice as in the native antigen, most of the epitopes recognized by antibodies are not continuous but assembled and brought into close apposition by folding of polypeptide chain.

c.         In contrast, the epitopes recognized by T lymphocytes are short, linear peptides.

d.         Synthetic peptides as potential vaccines:

7.         Immunogenic considerations

a.         Naturally acquired immunity to reinfection is virtually lifelong in the case of most of the viruses that reach their target organ(s) via systemic (viremic) spread.

b.         This solid immunity is attributable to antibody of IgG class, which successfully neutralizes the incoming challenge virus.

c.         Immunity to those respiratory and enteric viruses whose pathogenic effects are manifested mainly at the site of entry is attributable mainly to antibodies of the IgA class and tends to be of shorter duration.

d.         Thus the principal objective of artificial immunization by vaccine is to elicit a high titer of neutralizing antibodies of the appropriate class, directed against the relevant epitopes on the surface of the virion to prevent initiation of infection.

e.         It has proved difficult to produce effective vaccines against three classes of viral diseases: respiratory infections, sexually transmitted diseases, and persistent infections.

f.          Mucosal immunity:

i.          mediated by IgA; it is important in both respiratory and sexually transmitted diseases.

ii.          vaccination by the convenient oral route may generate satisfactory mucosal immunity in the respiratory and genital tracts, as a result of lymphocyte trafficking between different compartments.

g.         Special difficulties also attend vaccination against viruses known to establish persistent infections, such as herpesviruses and retroviruses.

h.         Subclinical infection is extremely effective, inducing life-long immunity following systemic infection.

8.         Passive Immunity

a.         Passive immunity is provided by the administration of preformed antibody in preparations called immune globulins.

b.         Passive-active immunity is induced by giving both immune globulins to provide immediate protection and a vaccine to provide long-term protection.

c.         Rabies immune globulin (RIG):

i.          it is used in the prevention of rabies in those who may have been exposed to the virus.

ii.          half the dose is infiltrated at the bite site and the other half given intramuscularly.

iii.         the preparation contains a high titer of antibody made by hyperimmunizing human volunteers with rabies vaccine.

d.         Hepatitis B immune globulin (HBIG):

i.          it is used in the prevention of hepatitis B in those who may have been exposed to the virus either by needle-stick or as a neonate born of a mother who is a carrier of HBV.

ii.          the preparation contains a high titer of antibody to hepatitis B virus and is obtained from humans to avoid hypersensitivity reactions.

iii.         HBIG is often used in conjunction with hepatitis B vaccine in passive-active immunization.

e.         Varicella-zoster immune globulin (VZIG):

i.          it is used in the prevention of disseminated zoster in those who may have been exposed to the virus and who are immunocompromised.

ii.          the preparation contains a high titer of antibody to varicella-zoster virus and is obtained from humans to avoid hypersensitivity reactions.

f.          Immune globulins (IG) are useful in the prevention of hepatitis A or measles in those who may have been exposed to these viruses.

g.         IG is commonly used prior to traveling to areas of the world where hepatitis A virus is endemic.

h.         IG contains pooled serum obtained from a large number of human volunteers who have not been hyperimmunized.