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| Safety and Efficacy of Primucell�-FIP Vaccine by F.W. Scott, DVM, Ph.D., W.V. Corapi, DVM, Ph..D., and C.W. Olsen, DVM, Ph.D. Cornell University |
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| Cornell Feline Health Center Cornell University College of Veterinary Medicine Feline Health Topics Newsletter (1991) An intranasal FIP vaccine, Primucell-FIP, was licensed and marketed within the United States in early 1991 by SmithKline Beecham Animal Health (SBAH, formerly Norden Laboratories). This vaccine is an attenuated temperature-sensitive (TS) mutant replication is partially restricted at 39�C but not restricted at 31�C. Three experiments were conducted in specific-pathogen-free (SPF) kittens to evaluate the safety and efficacy of this vaccine in a controlled laboratory setting. The results of these three studies were presented at the Fourth Annual Feline Practitioners Seminar at Cornell University on August 7-10, 1992. The following is a summary of the results as presented by the senior author. A full report of these studies will be published shortly. In the first experiment, the vaccine used was the modified live-virus FIP vaccine that was being field tested by SBAH prior to licensure. A single dose of vaccine (0.5 ml) was administered intranasally to each of 8 SPF kittens in the vaccine group (Group 1A) on day 0. No adverse effects were noted following vaccination. On day 28, the immunity of the vaccinates and 4 unvaccinated controls (Group 1B) was challenged via aerosol exposure to 103.0 tissue culture infectious doses -- 50% (TCID50) of virulent FIP virus strain 1146 (FIPV-1146). Four of the 8 vaccinates (50%) and 3 of 4 unvaccinated controls (75%) developed FIP within two months after challenge (Table 1). The remaining unvaccinated control cat had a febrile response after challenge followed by a long asymptomatic period. It eventually developed clinical FIP seven months after challenge. In the second experiment, eleven 16-week-old SPF kittens were vaccinated intranasally on days 0 and 28 with Primucell-FIP� (Group 2A). Four kittens were kept as unvaccinated contact controls (Group 2B) and 4 kittens were kept as unvaccinated, noncontact controls (Group 2C). Twenty-eight days after the second vaccination, the immunity of all cats was challenged by aerosol exposure with 105.0 TCID50 of virulent FIPV-1146. Ten of 11 vaccinates (91%) and 8 of 8 control cats (100%) developed FIP (Table 1). The third experiment was conducted jointly with scientists from SBAH. Thirty 16-week-old SPF kittens (Groups 3A, 3B, and 3E) were vaccinated at Cornell University with two doses of intranasal vaccine on days 0 and 28. An additional 9 kittens (Group 3G) were vaccinated at SBAH facilities in Lincoln, Nebraska with two doses of vaccine on days 0 and 28, using the same vaccine lot used at Cornell. Four additional groups of kittens (Groups 3C, 3D, 3F, and 3H) served as unvaccinated controls. On day 55 or 56, the immunity of all kittens was challenged by exposure to various doses of virulent virus (either FIPV-2246 or FIPV-DF2) given by various routes as listed in Table 1.. Groups 3A, 3B, 3C, and 3D were challenged at Cornell University with 105.5 TCID50 of FIPV-1146 either by aerosol or by intranasal drops. Cats in Groups 3E and 3F, which were shipped to SBAH at Lincoln following vaccination at Cornell University, as well as the cats vaccinated at SBAH (Group 3G) and their controls (Group 3H), were challenged at the Lincoln facility with 103.1 TCID50 of FIPV-DF2 by the oral route. All 21 vaccinates challenged with FIPV-1146 at Cornell University (Groups 3A, 3B) developed FIP during the 35 day observation period after challenge, while 6 of 9 unvaccinated controls (Groups 3C, 3D) developed FIP during this same period. With the FIPV-DF2 challenge given at SBAH, 2 of 8 Cornell-vaccinated cats (25%) in Group 3E and 3 of 6 unvaccinated controls (50%) in Group 3F developed FIP. For the SBAH vaccinates (Group 3G), 1 of 9 (11%) developed FIP compared to 3 of 4 unvaccinated controls (75%) in Group 3H following the low-dose FIPV-DF2 challenge. All vaccinated cats in the three studies developed positive-virus neutralizing antibody titers following vaccination. All but one of these vaccinated cats also had enhancing antibodies present in their sera following vaccination, as measured by in vitro assays for antibody-dependent enhancement (ADE) of FIPV infectivity of macrophages. Enhanced clinical disease, as evidenced by a fulminant and severe clinical disease pattern with a shorter time to euthanasia, was observed in 2 of 10 kittens (20%) in Group 3A challenged by aerosol exposure, and in 8 of 11 kittens (73%) in Group 3B challenged intranasally. None of the control cats in Groups 3C and 3D had enhanced disease. The safety of Primucell�-FIP has been monitored by SBAH through a field safety trial and by practitioner complaints. Post-vaccination complaints to SBAH and to the Cornell Feline Health Center have been minimal to date. Serious post-vaccination clinical signs of illness were not observed in the kittens comprising the three studies at Cornell University. In summary, with the challenge systems used in these studies, protection was only observed in a portion of the vaccinated cats challenged with the lower dose of virus (either FIPV-1146 or FIPV-DF2). With the higher dose FIPV-1146 challenge method using either aerosol or intranasal exposure, protection was not observed. Enhancement of infection occurred in several cases, especially with intranasal exposure. This was presumably due to a greater degree of exposure to virus via the intranasal route. The amount of FIP virus to which cats are exposed during natural infection in the field is unknown at this time. Studies in our laboratory have shown that ADE of infectivity of macrophages in vitro is a dose-related phenomenon between virus and enhancing antibodies. It appears that this same dose-related phenomenon exists with FIPV infection in vivo. Based on the limited efficacy and the potential to stimulate immune enhancement under certain conditions, the routine use of Primucell�-FIP in low-risk populations of cats cannot be recommended. In high-risk populations such as breeding catteries and open multicat facilities, the veterinarian must assess the risk of FIP without vaccination compared to the risk and benefits with vaccination. The veterinarian then should decide whether or not to establish a vaccination program in this population. |
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