Immunogenicity of an anti-clade B feline immunodeficiency fixed-cell virus vaccine in field cats

Abstract

Attempts at vaccine development for feline immunodeficiency virus (FIV) have been extensive, both because this is a significant health problem for cats and because FIV may be a useful vaccine model for human immunodeficiency virus. To date, only modest success, producing only short-term protection, has been achieved for vaccine trials in controlled laboratory settings. It is unclear how relevant such experiments are to prevention of natural infection. The current study used a vaccine that employs cell-associated FIV-M2 strain fixed with paraformaldehyde. Subject cats were in a private shelter where FIV was endemic, a prevalence of 29 to 58% over an 8-year observation period. Cats roamed freely from the shelter through the surrounding countryside but returned for food and shelter. After ensuring that cats were FIV negative, they were immunized using six doses of vaccine over a 16-month period and observed for 28 months after the initiation of immunization. Twenty-six cats (12 immunized and 14 nonimmunized controls) were monitored for a minimum of 22 months. Immunized cats did not experience significant adverse effects from immunization and developed both antibodies and cellular immunity to FIV, although individual responses varied greatly. At the conclusion of the study, 0 of 12 immunized cats had evidence of FIV infection, while 5 of 14 control cats were infected. Thus, the vaccine was safe and immunogenic and did not transmit infection. Furthermore, vaccinated cats did not develop FIV infection in a limited clinical trial over an extended time period. Thus, the data suggest that a fixed, FIV-infected cell vaccine has potential for preventing natural FIV infection in free-roaming cats.

FIG. 1

Experimental plan. Enrollment into the study began at −3 months, and time 0 marks the initiation of immunization. The experiment was terminated 28 months after the initial immunization.

FIG. 2

Titers of anti-FIV ELISA antibody in vaccinated cats at different time points postimmunization. Sera were tested against FIV-M2 antigen (●) and FIV-Pet antigen (■). The results are expressed as the reciprocal of the highest serum dilution that produced optical density readings higher than the average value obtained with 20 control FIV-negative sera plus three times the standard deviation. Sera that proved unreactive at a 1:100 dilution, the lowest dilution tested, are indicated as having titers of <100. Arrows indicate the times that vaccine boosters were administered to all cats.

FIG. 3

Anti-FIV WB profiles of vaccinated cats at different time points. Arrowheads indicate the times that vaccine boosters were administered. Results for positive and negative controls, as defined in the text, are shown at the left.

FIG. 4

Anti-FIV lymphoproliferative responses of vaccinated cats at different time points. The stimulation index was calculated as the ratio of [³H]thymidine incorporated by PBMC in the presence of FIV antigen to that in the presence of mock antigen. Arrows indicate the times that vaccine boosters were administered to all cats. Only a value of ≥2 was considered indicative of FIV-specific lymphoproliferation (broken lines). The mean stimulation index ± standard error for 23 assays carried out in the unvaccinated control cats that did not become infected was 1.6 ± 0.3.

FIG. 5

Phylogenetic analysis of FIV isolates cultured from two of the unvaccinated control cats that became infected during the course of the experiment (Gassata and Umberto). All other isolates have been previously described (26) except FIV-OMA, a nondomestic Pallas' cat FIV isolate (3) that was used as an outgroup. M and L followed by numbers indicate isolates obtained from the shelter prior to initiation of this experiment except for M2, which was isolated from a cat from the Pisa area but at a site distant from the shelter and which had no known contacts with cats at the shelter. Dots represent Italian isolates from other locations. Unnamed isolates are reference sequences. Fitch-Margoliash tree based on a 308-bp sequence (nucleotides 1130 to 1438) of the gag gene. Bootstrap values above 75 out of 100 are shown at branch points. Bar indicates the number of nucleotide substitutions per site.