Reprinted from the American Journal of Veterinary Research, May 1999 - Vol. 60 No. 5

Long-term immunity in cats vaccinated with an inactivated trivalent vaccine
Fred W. Scott, DVM, PhD, and Cordell M. Geissinger, BS

Objective—To evaluate duration of immunity in cats vaccinated with an inactivated vaccine of feline panleukopenia virus (FPV), feline herpesvirus (FHV), and feline calicivirus (FCV).

Animals— 17 cats.

Procedure—Immunity of 9 vaccinated and 8 unvaccinated cats (of an original 15 vaccinated and 17 unvaccinated cats) was challenged 7.5 years after vaccination. Specific-pathogen-free (SPF) cats were vaccinated at 8 and 12 weeks old and housed in isolation facilities. Offspring of vaccinated cats served as unvaccinated contact control cats. Virus neutralization tests were used to determine antibody titers yearly. Clinical responses were recorded, and titers were determined weekly after viral challenge.

Results—Control cats remained free of antibodies against FPV, FHV, and FCV and did not have infection before viral challenge. Vaccinated cats had high FPV titers throughout the study and solid protection against virulent FPV 7.5 years after vaccination. Vaccinated cats were seropositive against FHV and FCV for 3 to 4 years after vaccination, with gradually declining titers. Vaccinated cats were protected partially against viral challenge with virulent FHV. Relative efficacy of the vaccine, on the basis of reduction of clinical signs of disease, was 52%. Results were similar after FCV challenge, with relative efficacy of 63%. Vaccination did not prevent local mild infection or shedding of FHV or FCV.

Conclusions—Duration of immunity after vaccination with an inactivated, adjuvanted vaccine was > 7 years. Protection against FPV was better than for FHV and FCV.

Clinical Implications—Persistence of antibody titers against all 3 viruses for > 3 years supports recommendations that cats may be revaccinated against FPV-FHV-FCV at 3-year intervals. (Am J Vet Res 1999; 60:652 658)

The American Association of Feline Practitioners (AAFP) and Academy of Feline Medicine (AFM)'s Advisory Panel on Feline Vaccines recently developed the Guidelines for Feline Vaccination.1,2 In these guidelines, it was recommended that clinicians change from annual revaccination to revaccination at 3-year intervals after the first year for the standard triple-virus vaccine of cats (ie, feline panleukopenia virus [FPV], feline herpesvirus [FHV], and feline calicivirus [FCV]). Revaccination of cats at 3-year intervals initially was suggested 20 years ago,3 and in recent years, many investigators and several feline practitioners have become convinced that cats in the United States do not need to be vaccinated every year.4 Little scientific information, however, is available to substantiate this conviction for vaccines of cats, other than rabies vaccine. The AAFP-AFM Guidelines have caused considerable discussion within the veterinary profession.5-11

The FPV vaccines are among the best veterinary biologics. They produce excellent and rapid immunity characterized by persistent high neutralizing antibody titers.12-17 The FPV vaccines totally control the disease as long as cats are properly vaccinated after maternal immunity has waned.

The relative protection provided by attenuated or inactivated-adjuvanted FHV-FCV vaccines has been reported by several investigators.14,18-24 Viral challenge of immunity in all of these studies was performed shortly after vaccination, typically within a few weeks after the last vaccination. Because these 2 viruses initially cause mucosal infections with local disease, none of these parenterally administered vaccines prevent infection and shedding of virus, but they do greatly reduce local disease and protect vaccinated cats against serious systemic disease.

Duration of immunity after vaccination has not been evaluated for most veterinary biologics, with the exception of rabies vaccines. The vast majority of vaccines are evaluated for only short-term efficacy during a duration of a few weeks or months. Until recently, licensure of veterinary biologics did not require data on minimum duration of immunity, only that the vaccines were efficacious shortly after vaccination (weeks to a few months). Novel veterinary biologics now must have a minimal duration of immunity, but it is not required that maximum or actual duration of immunity be provided by the vaccine manufacturer. By tradition, manufacturers of veterinary biologics have recommended annual revaccinations, and veterinarians usually have adhered judiciously to this recommendation.

We previously reported the use of virus neutralization (VN) tests to determine antibody titers in 15 specific-pathogen-free (SPF) cats vaccinated as kittens with an inactivated triple vaccine.25 Cats were housed in strict isolation for up to 6 years. Booster vaccinations were not given to these cats, and unvaccinated control cats were housed in contact with vaccinated cats. We report here the extension of that study, including viral challenge of immunity in these cats at approximately 7.5 years after vaccination.

Materials and Methods
Cats—Thirty-two SPF cats were included in the study. The original 15 vaccinated cats (13 females, 2 males) were used to start a breeding colony. Seventeen female kittens born to the original queens were added to the breeding colony. Cats were maintained in isolation rooms, including 2 rooms containing several queens with 1 tom, 1 birthing room with separate cages, and 1 or more rooms for rearing weaned kittens. All cats had ad libitum access to dry commercial cat food.

Vaccine and vaccination—An inactivated commercially available triple vaccinea for FPV, FHV, and FCV was evaluated in the study. Production, contents, and characteristics of this vaccine have been reported elsewhere.25,26

The vaccine was administered SC to each of the original 15 kittens when they were 8 and 12 weeks old. These kittens were moved to the new SPF breeding colony when they were 5 months old. Additional booster vaccinations were not given to these cats during the 7.5 years of the study. Additional breeding cats reared from the original queens were never vaccinated and served as unvaccinated contact control cats from year 1 until the end of the study.

Serologic testing—Blood samples from vaccinates and control cats were collected in evacuated glass tubes 2 months and 3, 4, 5, 6, and 7 years after vaccination, immediately before each viral challenge, and at weekly intervals for 4 weeks after each viral challenge. Serum was separated from clotted blood samples and stored at 20 C until assayed (ie, VN tests) for antibody against FPV, FHV, and FCV.25 Samples obtained at 7 years and those obtained after viral challenge were assayed for each cat as a unit on the same day. This was repeated for each of the 3 viruses.

Surveillance of the SPF colony—During the nearly 8 years of the study, cats in the SPF colony were monitored daily for evidence of disease, but clinical signs of infectious diseases were not observed. During the fifth year of the study, representative cats in the colony were tested extensively, using serologic analysis and bacterial and viral culture, to detect evidence of known infectious agents. With the exception of titers against FPV, FHV, and FCV in vaccinated cats, results for all serologic and culture assays for viruses and bacterial pathogens were negative.

Viral challenge of immunity—Nine of the original vaccinated cats and 8 of the original unvaccinated control cats remained in the breeding colony 7.5 years after onset of the study. These 17 cats were transferred to an isolation room equipped with filter-type isolation cages. Cats were randomly allotted to cages (2 cats/cage) and allowed to acclimate for 2 weeks. An implantable identification and temperature chip was injected into the subcutaneous tissue in the area of the shoulder in each cat. This chip was programmed with each cat's specific ear tag number, which enabled rapid identification of the cat and recording of the cat's body temperature with a special hand-held computer attached to a recorder wand that was passed over the shoulder area and the implanted chip.

At monthly intervals, immunity of these cats was challenged sequentially by use of virulent strains of FPV, FHV, and FCV. Body temperatures were recorded daily via the implanted chip, and clinical signs were evaluated and scored daily for 14 days after each viral challenge. Each day, clinical signs for each cat were evaluated and assigned a clinical score of 0 to 4 on the basis of perceived severity (0 = clinically normal; 1 = slight; 2 = moderate; 3 = serious; 4 = severe). Clinical signs evaluated included conjunctivitis, ocular discharge, rhinitis (serous nasal discharge, mucopurulent nasal discharge), sneezing, dyspnea, rales, coughing, enteritis, lethargy, inappetence, dehydration, lingual and oral ulcers, external ulcers, and "other." Body temperature was converted to a clinical score (< 39.5 C = 0; 39.5 to 39.9 C = 1; 40.0 to 40.4 C = 2; 40.5 to 40.9 C = 3; > 41.0 C = 4). Daily and cumulative clinical scores for each cat were calculated, and mean daily clinical scores, cumulative clinical scores, and mean cumulative clinical scores for the vaccinated group and the unvaccinated control group were calculated.

Challenge with FPV—"Immunity against FPV was tested in all 17 cats, using the USDA FPV-ICK33 challenge virus.27 Each cat received 1.0 ml containing 106.5 TCID50 of challenge virus (day 0); 0.5 ml was administered intranasally and 0.5 ml was administered orally. An aliquot of the challenge virus was removed prior to administration, and it along with another aliquot of the virus remaining after administration were frozen and assayed to confirm the actual dose of virus given to each cat.

Samples were collected for virus isolation testing, including blood samples on days 3, 5, and 7 and rectal swab specimens on days 0, 3, 5, 7, and 11. Samples were frozen until assayed in Crandell feline kidney (CrFK) cell cultures. Blood samples were passaged 3 times in culture, and rectal swab specimens were passaged twice. Samples positive for virus were titrated in cell culture to determine the quantity of virus.

Blood samples for WBC counts were obtained 8, 3, and 0 days before viral challenge and 3, 5, 7, 11, and 14 days after viral challenge. Samples were assayed at the clinical pathology laboratory at our facility. Serum samples were obtained 0, 7, 14, and 28 days after challenge for use in VN testing to determine antibody titers.

Challenge with FHV—One month after FPV challenge, immunity against FHV was tested in all 17 cats. Each cat received 1.0 ml containing 105.5 TCID50 of the USDA National Veterinary Services Laboratory (NVSL) FHV challenge virus (day 0); 0.5 ml was administered intranasally and 0.5 ml was administered orally. As described for FPV, pre- and postchallenge aliquots of the virus were assayed in CrFK cell cultures to confirm the actual dose of challenge virus administered to the cats.

Pharyngeal swab specimens for use in virus isolation and titration were collected on days 0, 4, 6, 8, 11, and 14 after viral challenge. Swab specimens were frozen at -60 C until assayed by twofold virus titration in CrFK cell cultures in 96-well plates. Serum samples were obtained on days 0, 6, 8, 11, 14, 21, and 27 after viral challenge and were assayed for antibody titers by using

VN tests. Challenge with FCV—One month after FHV challenge, immunity against FCV was tested in 16 remaining cats.28,29 Each cat received 1.0 ml containing 106.0 TCID50 of the USDA NVSL FCV-255 challenge virus (day 0); 0.5 ml was administered intranasally and 0.5 ml was administered orally. As described for FPV, pre- and postchallenge aliquots of the virus were assayed in CrFK cell cultures to confirm the actual dose of challenge virus administered to the cats.

Pharyngeal swab specimens for use in virus isolation and titration were collected on days 0, 2, 5, 7, 9, and 14 after viral challenge. Swab specimens were frozen at -60 C until assayed by twofold virus titration in CrFK cell cultures in 96-well plates. Serum samples were obtained on days 0, 5, 7, 9, 14, 21, and 33 after viral challenge and assayed for antibody titers by using VN tests.

Results
Serologic tests Antibody titers against FPV, FHV, and FCV in the sera samples of the 15 vaccinated and 17 unvaccinated contact control cats for the first 6 years of the study have been reported.25 Mean antibody titers against these 3 viruses were summarized (Fig 1).

Figure 1—Mean antibody titers against feline panleukopenia virus (FPV), feline herpesvirus (FHV), and feline calicivirus (FCV) for 15 specific-pathogen-free (SPF) cats vaccinated as kittens with 2 doses of an inactivated, adjuvanted vaccine. Results were determined by use of virus neutralization tests. Values for year 1 represent samples obtained 2 months after vaccination. Yellow = FPV. Red = FHV. Green = FCV.
  
Figure 3—Mean antibody titers against FHV in 9 vaccinated (Yellow) and 8 unvaccinated control (Red) SPF cats exposed to virulent FHV 7.5 years after vaccination. Notice the dramatic anamnestic antibody response in vaccinated cats, compared with the response in unvaccinated control cats.

Figure 2—Mean antibody titers against FPV in 9 vaccinated (Yellow) and 8 unvaccinated control (Green)
 
Figure 4—Mean antibody titers against FCV in 9 vaccinated (Yellow) and 7 unvaccinated control (Green) SPF cats exposed to virulent FCV 7.5 years after vaccination. Notice the anamnestic antibody response in vaccinated cats, compared with the response in unvaccinated control cats.
Viral challenge of immunity with virulent FPV 7.5 years after vaccination resulted in an increase in mean FPV antibody titers 7, 14, and 28 days after viral challenge (Fig 2). All 8 unvaccinated control cats were seronegative (titers of < 1:10) on the day of viral challenge. Six of 8 had low positive titers (mean, 1:28) on day 7 after viral challenge, but titers increased dramatically by days 14 (mean, 1:3,438) and 28 (mean, 1:8,125) after viral challenge.

Seven years after vaccination, 6 of 10 vaccinated cats were seropositive to FHV, but only 1 of 9 vaccinated cats was seropositive to FHV at the time of FHV challenge 7.5 years after vaccination. On day 6 after viral challenge, all 9 cats were seropositive (mean titer, 1:9). By day 8 after viral challenge, titers had increased sharply (mean, > 1:242), and 7 of 9 cats had titers of > 1:256 (Fig 3). Titers remained high on days 11, 14, 21, and 27, with all vaccinated cats having titers of > 1:256 (the highest dilution tested in these assays) on day 11 after viral challenge. By contrast, all unvaccinated control cats were seronegative to FHV on days 6 and 8 after viral challenge, and 2 of 7 remained seronegative on day 11. Mean titers for the control cats were 1:3 on day 11, 1:13 on day 14, and 1:11 on days 21 and 27 after viral challenge. Thus, peak mean FHV antibody titer after viral challenge was approximately twentyfold higher for the vaccinated group, compared with titers for the unvaccinated control group.

Figure 5—Mean leukocyte counts in 9 vaccinated (Yellow) and 8 unvaccinated control (Green) SPF cats exposed to virulent FPV 7.5 years after vaccination.
  
Figure 7—Clinical response of 9 vaccinated (Green) and 8 unvaccinated control (Yellow) SPF cats exposed to virulent FHV 7.5 years after vaccination. Clinical score was determined on the basis of perceived severity (0 = clinically normal; 1 = slight; 2 = moderate; 3 = serious; 4 = severe) for clinical signs that included conjunctivitis, ocular discharge, rhinitis (serous nasal discharge, mucopurulent nasal discharge), sneezing, dyspnea, rales, coughing, enteritis, lethargy, inappetence, dehydration, lingual and oral ulcers, external ulcers, and "other."

Figure 6—Mean lymphocyte counts in 9 vaccinated (Yellow) and 8 unvaccinated control (Green) SPF cats exposed to virulent FPV 7.5 years after vaccination.
  
Figure 8—Clinical response of 9 vaccinated (Green) and 7 unvaccinated control (Yellow) SPF cats exposed to virulent FCV 7.5 years after vaccination. See Fig 7 for key.

At the time of FCV challenge 7.5 years after vaccination, 6 vaccinated cats were seronegative to FCV. After FCV challenge, mean antibody titers against FCV in vaccinated cats were 1:2, 1:70, 1:130, and 1:400 on days 5, 7, 9, and 14, respectively (Fig 4). By contrast, the 7 control cats at the time of challenge were seropositive on day 7 (mean titer, 1:9), with the mean titer increasing to 1:33 on day 9 and peaking at 1:38 on day 14. Peak mean titer after FCV challenge for the vaccinated cats was approximately tenfold greater than that for the unvaccinated control cats.

Challenge with FPV—All 17 cats remained healthy throughout the postchallenge period. Signs of illness or fever were not observed.

Mean total leukocyte counts were determined on selected days from 8 days before to 14 days after FPV challenge (Fig 5). Mean leukocyte counts for the 9 vaccinated cats remained unchanged after viral challenge; mean of the mean counts for the 3 prechallenge days was 8,180 cells/µl, compared with 8,030 cells/µl for the 5 selected postchallenge days. Mean of the mean counts for the 8 unvaccinated control cats decreased from 7,300 cells/µl before viral challenge to 5,710 cells/µl after viral challenge, with the lowest mean count (4,760 cells/µl) on day 7 after viral challenge. Total lymphocyte counts for these 17 cats mimicked total leukocyte counts, with typical counts for the vaccinated cats and decreased counts for the unvaccinated control cats after viral challenge (Fig 6). Mean of the mean lymphocyte counts for vaccinates was 1,990 cells/µl for the 3 selected prechallenge days and 1,900 cells/µl for the 5 selected days after viral challenge. For the unvaccinated control cats, values were 2,150 cells/µl before viral challenge and 1,360 cells/µl after viral challenge, with mean values of 900 cells/µl on day 5 and 880 cells/ml on day 7 after viral challenge.

Viral isolation from blood samples and rectal swab specimens was attempted after FPV challenge. Blood samples for each cat were tested for FPV on days 3, 5, and 7, but virus was isolated from only 1 cat on the second passage of the blood sample in cell culture. Rectal swab specimens were tested for FPV on days 0, 3, 5, 7, and 11 after viral challenge. It was not possible to determine whether there was virus in these rectal swab specimens during the first passage in cell culture. A small amount of virus (101.7 TCID50/ml) was detected in only 2 of 9 vaccinated cats on the second passage and only in specimens obtained on day 7. Virus was not isolated from the other 7 vaccinated cats throughout the observation period. By contrast, 6 of 8 unvaccinated control cats were shedding virus, as determined by viral isolation testing of the rectal swab specimens. Four of these cats had titers in the second cell culture passage of > 104 TCID50/ml in specimens obtained on day 7 after viral challenge.

Challenge with FHV—Clinical response of the 17 cats challenged with virulent FHV was summarized (Fig 7). All 17 cats developed clinical signs of disease (feline viral rhinotracheitis) consistent with FHV infection. All vaccinated cats recovered from infection without complications, as did 7 of 8 unvaccinated control cats. However, 1 control cat developed severe disease on day 6 and died later that day despite supportive treatment. Mean cumulative clinical score was 22.7 for vaccinated cats and 46.9 for unvaccinated control cats. Thus, total clinical response for the unvaccinated control cats was approximately twice that of the vaccinated cats. On the basis of reduction of clinical signs of disease, the vaccine had a relative efficacy (ie, preventable fraction) of 52% against FHV challenge 7.5 years after vaccination.

After FHV challenge, virus was isolated from pharyngeal swab specimens obtained from 6 of 9 vaccinated and 7 of 8 unvaccinated control cats. In cats that shed virus, there was not a detectable difference in the amount of virus or duration of virus shedding between the 2 groups of cats.

Challenge with FCV—Clinical response of the 16 cats challenged with virulent FCV was summarized (Fig 8). One vaccinated cat did not have clinical signs of illness. Three vaccinated cats were febrile for a single day as the only clinical response, and another vaccinated cat was inappetant for 3 days as the only clinical sign. Oral ulcers were observed in 4 vaccinated cats as the primary clinical response; ulcers lasted for 3 to 10 days. In the unvaccinated control cats, oral or nasal ulcers were observed in 6 of 7 cats. Signs of systemic illness, including inappetence or lethargy, were observed in 5 of 7 control and 2 of 9 vaccinated cats. Mean cumulative clinical response was 2.7 times greater for unvaccinated control cats (21.9), compared with vaccinated cats (8.1). On the basis of reduction of clinical signs of disease, the vaccine had a relative efficacy of 63% against FCV disease 7.5 years after vaccination.

All cats shed virus into the oropharynx on days 2 and 5 after FCV challenge, and all but 1 vaccinated and 1 control cat shed virus on day 7. By day 9 after viral challenge, the amount of virus shed decreased dramatically, with only 1 vaccinated and 3 control cats having positive results on viral isolation testing. There was little or no difference in the quantity of virus or duration of viral shedding between the 2 groups of cats.

Discussion
Similar to antibody titers for the first 6 years of the study,25 antibody titers against FPV for these vaccinated cats remained high throughout the study reported here. Titers against FPV did not decrease to < 1:500 for any vaccinate during the first 6 years after vaccination. Mean antibody titer only decreased from 1:6,923 (n = 13) 2 months after vaccination to 1:4,769 (n = 13) by 5 years and to 1:5,312 (n = 8) by 6 years after vaccination. In essence, FPV antibody titers did not decrease during the initial 6 years after vaccination. Concurrently, unvaccinated contact control cats remained free of antibodies against FPV and, hence, free of FPV infection within the colony. Antibody titers against FPV remained high for at least 7.5 years after vaccination, and these antibodies provided solid and complete protection against viral challenge with virulent FPV.

The FPV antibody titers for all 4 sets of weekly serum samples obtained after FPV challenge for the 9 vaccinated and 8 unvaccinated control cats, and the year 7 samples (Fig 1), were assayed on the same day against 500 TCID50 of test virus, instead of the standard 30 to 100 TCID50. This resulted in titers up to tenfold lower for all seropositive cats than would have been expected if the standard dose of reference virus had been used. This inverse 1:1 association of antibody titer-to-dose of test FPV has been reported elsewhere by the senior author (FWS).30

Susceptible adult cats, especially SPF cats, often do not exhibit clinical signs of disease after viral challenge with virulent FPV, despite infection and shedding of virus. Decreases in total leukocyte and lymphocyte counts, seroconversion to FPV, and shedding of virus in the feces often are the only markers of infection. Other studies in our laboratory31,32 established that clinical signs of disease as a result of FPV infection were dependent on mitotic activity of the crypt cells in the small intestine, and that gnotobiotic and SPF kittens (whose mitotic activity of crypt cells was low when compared with typical cats) became infected and seroconverted without clinical signs of disease. Therefore, results obtained in this study after FPV challenge of unvaccinated susceptible adult SPF cats (eg, leukopenia, viral shedding, and seroconversion without clinical signs of disease) were expected.

As reported elsewhere,25 all 13 vaccinated cats tested were seropositive to FHV 2 months after vaccination (mean titer, 1:18). Mean titers declined to 1:12 (n = 15) at 3 years, 1:9 (n = 14) at 4 years, 1:4 (n = 13) at 5 years, and 1:2 at 6 (n = 8) and 7 (n = 10) years after vaccination. Four of 14 cats tested at year 4 were seronegative (titer of < 1:2), but 3 of these 4 had low titers (1:2) at year 5. The other seronegative cat had a titer of 1:4 at year 5 and a low titer (1:2) at year 6. Four of 8 vaccinates tested were seropositive to FHV 6 years after vaccination.

Reports19,20 on various FHV vaccines indicate that detectible antibody (titer of > 1:2) is sufficient to provide substantial protection. In all vaccinated cats tested in those studies, a rapid anamnestic antibody response was detectable by 7 days after challenge-exposure, even in cats that had FHV titers of < 1:2 at the time of viral exposure. Unvaccinated control cats did not have detectable antibody titers 7 days after viral exposure, even when they had clinical signs typical of feline viral rhinotracheitis. In 1 study,20 40 kittens were vaccinated with a monovalent FHV vaccine, and 10 were unvaccinated control kittens. Mean titer in vaccinates increased rapidly from a mean of 1:40 at the time of viral challenge to 1:237 on day 7 and 1:600 on day 14 after challenge-exposure. By contrast, mean antibody titers of the10 unvaccinated kittens were 0 on the day of challenge-exposure and day 7 after challenge-exposure. By 14 days after viral challenge, mean titer of the unvaccinated kittens was only 1:26, which was much less than that of the 40 vaccinated kittens. The rapid anamnestic response in cats challenge-exposed 7.5 years after vaccination in the study reported here was similar to that observed in those previous studies in which viral challenge was performed a few weeks after vaccination.

The study reported here confirmed that FHV antibody titers last for > 3 years after vaccination. Because an inactivated vaccine was used in this study, the persistence of antibody titers is assumed to result from establishment of memory B cells that enable maintenance of a continued low antibody titer.33 These memory B cells quickly proliferate and differentiate into effector cells after exposure to FHV antigens, resulting in rapid production of antibodies against FHV. The rapid and dramatic anamnestic antibody response against FHV in all 9 vaccinated cats after viral challenge (Fig 3) clearly documented that there were memory B cells in these vaccinated cats 7.5 years after vaccination, even in cats without a detectable antibody titer at the time of viral challenge.

Povey et al14 conducted a study with the same inactivated triple vaccine as the one tested in the study reported here. In that study, SPF cats were vaccinated twice, IM, at a 3-week interval and then challenge-exposed with 105.7 TCID50 of virulent strain of FHV-1 3 weeks after the second vaccination. Mild disease developed in 9 of 20 vaccinates (mean cumulative clinical score, 1.1), and typical disease developed in all 10 unvaccinated cats (mean cumulative clinical score, 22.2). The relative efficacy against FHV 3 weeks after vaccination was 95% on the basis of mean cumulative clinical scores. Fourteen of 20 vaccinated cats shed small quantities of FHV after viral challenge, compared with larger quantities of FHV shed by all 10 control cats. Comparing results of that study with results of the study reported here, relative efficacy of the vaccine against FHV decreased from 95% 3 weeks after vaccination to 52% 7.5 years after vaccination.

We reported elsewhere19 an evaluation of the safety and efficacy of a FHV-FCV modified-live-virus vaccine. Kittens were given 2 doses of attenuated-virus vaccine, IM, and challenge-exposed with virulent FHV 5 to 7 weeks after the second dose of vaccine. Mean cumulative clinical score was 1.1 for vaccinated and 6.6 for control kittens. That correlates to a relative efficacy of 83%, which compares with 52% 7.5 years after vaccination in the study reported here.

All vaccinated cats were seropositive to FCV 2 months after vaccination (mean titer, 1:145).25 Titers gradually decreased over time, with a mean titer of 1:45 (n = 13) at year 5 but a mean titer of only 1:8 at year 6. All vaccinates were seropositive to FCV at year 4, and only 1 vaccinated cat was seronegative (titer, < 1:2) at year 5. That cat was again seropositive (titer, 1:4) at year 5 and remained seropositive (titer, 1:2) at year 6. One of 8 cats tested at year 6 was seronegative to FCV, although 3 additional cats had low titers of 1:2.

Analysis of results of this study clearly indicate that good FCV antibody titers persist for at least 4 years after vaccination. We and others have observed that FCV antibody titers are consistent with substantial protection against virus exposure. Similar to FHV, immunity is not 100%, with infection and viral shedding developing in vaccinated cats. In this study, viral challenge of vaccinated cats 7.5 years after vaccination resulted in partial protection, with reduced clinical signs of disease but without reduction in infection and shedding of virus. Clinical signs of disease in vaccinated cats tended to be restricted to superficial infection such as ulcers, whereas disease in unvaccinated control cats tended to be systemic as well as local. Protection against FCV was somewhat better than that for FHV.

In the study by Povey et al,14 mild disease consisting of fever or oral ulcers developed in 17 of 20 cats given viral challenge with FCV-255 via aerosol exposure. Mean cumulative clinical score for vaccinated cats after viral challenge was 2.7, compared with 17.5 for unvaccinated control cats. Relative efficacy for this vaccine against FCV was 85%. There was not a reduction of the quantity of virus shed in vaccinated cats, compared with unvaccinated control cats, after FCV challenge. Comparing results for that study with results for the study reported here, relative efficacy of this vaccine against FCV, on the basis of reduction of clinical signs of disease, decreased from 85% 3 weeks after vaccination to 63% 7.5 years after vaccination.

In our previous study of FHV and FCV,19 kittens were given 2 doses of an attenuated-virus vaccine, IM, and challenge-exposed with virulent FCV-255 2 to 4 weeks after the second dose of vaccine. Vaccinated cats did not develop serious systemic disease, but the unvaccinated control cats did; however, many of the vaccinated cats became febrile and developed small oral ulcers. Mean cumulative clinical score was 2.5 for vaccinated and 7.0 for unvaccinated control cats. Relative efficacy in that study was 64%, remarkably similar to the 63% obtained 7.5 years after vaccination in the study reported here.

This study confirmed that vaccination of kittens with an inactivated, adjuvanted FPV-FHV-FCV vaccine produced long-lasting antibody titers against these 3 viruses, with titers persisting for > 3 years in vaccinated cats. The FPV-neutralizing antibodies persisted in vaccinated cats for > 7 years and may well persist for life in properly vaccinated cats. Titers against FHV and FCV gradually decreased over time but persisted for > 3 years. Memory cells for neutralizing antibodies against FHV and FCV persisted for > 7 years in vaccinated cats.

On the basis of results of the study reported here, results of rabies vaccine studies in cats that document solid protection for 3 years,34 and information from human medicine, it would appear reasonable to modify the recommendations for routine vaccination of cats in moderate- to low-risk populations. In our opinion, cats that are properly vaccinated as kittens should be revaccinated with a single dose of triple vaccine at 1 year old, then revaccinated every 3 years thereafter with a triple (ie, FPV-FHV-FCV) or a dual (ie, FHV-FCV) vaccine. These recommendations are consistent with those in the Guidelines for Feline Vaccination from the AAFP-AFM.1,2

aFel-O-Vax PCT, Fort Dodge Laboratories, Fort Dodge, Iowa.

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