Feline Immunodeficiency Virus Vaccine Research Articles

Densitometric analysis of Western blot assays for feline immunodeficiency virus antibodies

Western blot (WB) strips for antibodies directed to feline immunodeficiency virus (FIV) were analysed using reflectance densitometry by a semiautomatic densitometer. This method was used to quantify the antibody responses to different FIV proteins in both vaccinated and naturally or experimentally-infected cats. In order to increase reproducibility, reagents and protocols were accurately standardised and internal controls were added. In a first format, an internal control band consisting of feline IgG was added to each blot to minimise the effect of band intensity variation. In a second format, antibody concentrations were calculated from the ratio of the densities produced by test sera and by positive and negative standard sera. The sera under scrutiny were also examined by standard enzyme-linked immunosorbent assay (ELISA) and the results obtained compared with those of the corresponding WB. A statistically significant positive correlation was found between the results obtained with the two methods, and this was especially evident when ELISA titres were compared to corrected WB values ( P=0.001). Densitometric analysis of WB assays allowed to quantify the antibodies against FIV proteins and might be useful to investigate possible humoral immune correlates of protection in FIV vaccination studies and antibody production in the early phase of infection. The quantitation of antibodies to Gag and Env FIV antigens might be used to obtain further informations on the course of FIV disease, as previously demonstrated in human immunodeficiency virus-1 (HIV-1) infections.

Vaccination of cats against feline immunodeficiency virus (FIV): a matter of challenge

So far, most apparently successful immunodeficiency virus vaccines have only been tested against challenge with cell culture-adapted virus. However, even live priming of cats with feline herpesvirus (FHV) vectors expressing the FIV gag and env gene followed by inactivated booster vaccination with fixed FIX infected cell vaccine proved non-protective against infection with a primary FIV isolate. An effective FIV vaccine for field applications therefore is still not underway.

Suppression of feline immunodeficiency virus replication in vitro by a soluble factor secreted by CD8+ T lymphocytes.

Mitogen-activated lymphoblasts isolated from the blood and lymph nodes, but not the spleen, of domestic cats acutely infected with the Petaluma or Glasgow8 isolates of feline immunodeficiency virus (FIV), suppressed the replication of FIV in the MYA-1 T-cell line in a dose-dependent manner. This effect was not limited to the homologous isolate of FIV. The suppressor activity declined with progression to chronic infection, with lower levels of activity detectable only in the lymph nodes. Immunization of domestic cats with whole inactivated FIV vaccine elicited profound suppressor activity in both the blood and lymph nodes. The suppressor activity was associated with the CD8+ T-cell subpopulation, the effect did not appear to be major histocompatibility complex-restricted, and was mediated by a soluble factor(s). This activity may be associated with the control of virus replication during both the asymptomatic stages of FIV infection, and in the protective immunity observed in cats immunized with whole inactivated virus vaccines.

Analysis of the protective immunity induced by feline immunodeficiency virus vaccination

This chapter discusses the analysis of the protective immunity induced by feline immunodeficiency virus (FIV) vaccination. Since its discovery in 1986, FIV infection has been shown to result in an immunodeficiency in cats that is similar to AIDS in human beings. The virus is now recognized as a long-established and important feline pathogen and an appropriate animal model for human immunodeficiency virus (HIV) infection, playing a key role in the development of vaccines against HIV. Furthermore, because FIV induces significant disease in cats, the development of an effective FIV vaccine is of great veterinary interest. Protection against FIV infection has been achieved by immunizing cats with a whole inactivated virus (WIV) vaccine produced from the FL4 feline lymphoblastoid cell line, which is persistently infected with the Petaluma isolate of FIV (FIV/PET). This cell line appears to be unique, because it produces large amounts of FIV/PET rich in envelope glycoprotein (Env) that is well preserved during purification.

Vaccination with experimental feline immunodeficiency virus vaccines, based on autologous infected cells, elicits enhancement of homologous challenge infection.

Cats were vaccinated with fixed autologous feline immunodeficiency virus (FIV)-infected cells in order to present viral proteins to the immune system of individual cats in an MHC-matched fashion. Upon vaccination, a humoral response against Gag was induced. Furthermore, virus-neutralizing antibodies were detected in a Crandell feline kidney cell-based neutralization assay, but not in a neutralization assay based on primary peripheral blood mononuclear cells. Despite the induction of these FIV-specific responses, vaccinated cats were not protected. Instead, accelerated virus replication was found, an observation similar to what previous experiments using other vaccine candidates have shown. Here, the results of the present study are discussed in the light of enhancement of lentivirus infections as a complicating factor in lentivirus vaccine development.

Autologous and heterologous neutralization analyses of primary feline immunodeficiency virus isolates.

Feline immunodeficiency virus (FIV) provides a model system with which the significance of neutralizing antibody (NA) in immunosuppressive lentivirus infections may be studied. To date, no detailed analysis of the neutralization properties of primary FIV isolates has been reported. In this study, we have conducted the first comprehensive study of the sensitivity to autologous and heterologous neutralization in a lymphoid cell-based assay of 15 primary FIV isolates and, for comparison, of one tissue culture-adapted strain. Primary isolates in general proved highly NA resistant, although there was considerable individual variation. Variation was also observed in the capacity of immune sera to neutralize heterologous FIV isolates. The ability of sera to neutralize isolates or for isolates to be neutralized by sera did not correlate with epidemiological and genetic relatedness or with the quasispecies complexity of the isolates. From the study of specific-pathogen-free cats experimentally infected with viral isolates associated with NA of different breadths, it appears that the development of FIV vaccines cannot rely on the existence of viral strains inherently capable of inducing especially broad NA responses.

Efficacy evaluation of prime-boost protocol: canarypoxvirus-based feline immunodeficiency virus (FIV) vaccine and inactivated FIV-infected cell vaccine against heterologous FIV challenge in cats.

To evaluate the immunogenicity and prophylactic efficacy of immunization schemes employing a recombinant canarypoxvirus ('ALVAC')-based feline immunodeficiency virus (FIV) vaccine alone or in combination with an inactivated FIV-infected cell vaccine against homologous and heterologous FIV challenges in cats. Specific pathogen-free cats were given a total of three immunizations with subtype A vaccines and challenged 4 weeks after the final immunization with 50 median animal infectious doses (ID50) of FIV-Petaluma, a subtype A isolate. Following the initial challenge, protected cats received a second challenge with 75 ID50 of FIV-Bangston, a subtype B isolate. FIV-specific humoral and cell-mediated responses were measured to determine the immune correlates of protection. Two of three cats immunized with the ALVAC FIV recombinants alone were protected from homologous FIV challenge in the presence of FIV-specific cytotoxic T-lymphocyte (CTL) responses but in the absence of FIV-specific humoral responses. All three cats immunized with the ALVAC-FIV recombinant and boosted with FIV-infected cell vaccine were also protected from homologous FIV challenge in the presence of both FIV-specific CTL and humoral responses. Partial to full protection was observed in ALVAC-FIV/FIV-infected cell vaccine-immunized cats against a heterologous FIV challenge given 8 months after the initial challenge. Two out of three cats had transient infection and the remaining cat had no sign of FIV infection at a dose at which all three control cats were readily infected. Immunization schemes employing ALVAC-based FIV vaccines in combination with inactivated FIV-infected cell vaccine generate protective immune responses that can cross-react with FIV isolates that are genetically distinct from the vaccine strains.

Perspectives on FIV vaccine development

Feline immunodeficiency virus (FIV), discovered a decade ago, is the causative agent of feline immunodeficiency syndrome (FAIDS), a chronically degenerative, fatal disease in domestic cats. Our understanding of the immunopathogenesis of FIV has improved but the development of an effective therapy and prophylaxis has been slow, reflecting the remarkable adaptability of the virus to modern medical intervention. FIV vaccine development has had its successes and failures similar to those encountered in human immunodeficiency virus (HIV) vaccine research. This review summarizes the status of FIV vaccine research, including trials of conventional, recombinant subunit and recombinant vector-based vaccines, and potential mechanisms of vaccine protection. The lessons learned from the FIV model should provide new insights for the approaches toward the development of HIV vaccines.

Development of FIV-specific cytolytic T-lymphocyte responses in cats upon immunisation with FIV vaccines

Vaccine protection has been achieved in cats against experimental infection with feline immunodeficiency virus (FIV). Such protection has been attributed to FIV-specific humoral immunity, as well as cellular immunity of unknown mechanism(s). Since cell-mediated immunity plays a crucial role in the clearance of viral infections, this study evaluated the role of FIV-specific CTL in vaccine prophylaxis. Cats were immunised with inactivated FIV vaccines, reported to have >90% vaccine efficacy. Significant levels of specific CTL activity were detected following the third immunisation. CTL activity persisted for several months and could be enhanced through a booster immunisation. The levels of CTL activity were comparable to those induced by a recombinant canarypoxvirus based FIV vaccine. These results suggest a possible role for CTL-mediated immunity in vaccine protection against FIV infection in cats.

Parameters of disease progression in long-term experimental feline retrovirus (feline immunodeficiency virus and feline leukemia virus) infections: hematology, clinical chemistry, and lymphocyte subsets.

After several years of latency, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was to determine laboratory parameters characteristic of disease progression which would allow a better description of the asymptomatic phase and a better understanding of the pathogenesis of the two infections. Therefore, experimentally infected cats (FIV and/or FeLV positive) and control animals were observed over a period of 6.5 years under identical conditions. Blood samples were analyzed for the following: complete hematology, clinical chemistry, serum protein electrophoresis, and determination of CD4+ and CD8+ lymphocyte subsets. The following hematological and clinical chemistry parameters were markedly changed in the FIV-infected animals from month 9 onwards: glucose, serum protein, gamma globulins, sodium, urea, phosphorus, lipase, cholesterol, and triglyceride. In FeLV infection, the markedly changed parameters were mean corpuscular volume, mean corpuscular hemoglobin, aspartate aminotransferase, and urea. In contrast to reports of field studies, neither FIV-positive nor FeLV-positive animals developed persistent leukopenia, lymphopenia, or neutropenia. A significant decrease was found in the CD4+/CD8+ ratio in FIV-positive and FIV-FeLV-positive animals mainly due to loss of CD4+ lymphocytes. In FeLV-positive cats, both CD4+ and, to a lesser degree, CD8+ lymphocytes were decreased in long-term infection. The changes in FIV infection may reflect subclinical kidney dysfunction, changes in energy and lipid metabolism, and transient activation of the humoral immune response as described for human immunodeficiency virus (HIV) infections. The changes in FeLV infection may also reflect subclinical kidney dysfunction and, in addition, changes in erythrocyte and immune function of the animals. No severe clinical signs were observed in the FIV-positive cats, while FeLV had a severe influence on the life expectancy of persistently positive cats. In conclusion, several parameters of clinical chemistry and hematology were changed in FIV and FeLV infection. Monitoring of these parameters may prove useful for the evaluation of candidate FIV vaccines and antiretroviral drugs in cats. The many parallels between laboratory parameters in FIV and HIV infection further support the importance of FIV as a model for HIV.

Feline immunodeficiency virus vaccination: characterization of the immune correlates of protection.

Whole inactivated virus (WIV) vaccines derived from the FL4 cell line protect cats against challenge with feline immunodeficiency virus (FIV). To investigate the correlates of protective immunity induced by WIV, we established an immunization regimen which protected a proportion of the vaccinates against challenge. A strong correlation was observed between high virus neutralizing antibody titers and protection following challenge. To investigate further the immune mechanisms responsible for immunity, all of the vaccinates were rechallenged 35 weeks following the initial challenge. Results of virus isolation from peripheral blood mononuclear cells indicated that 9 of 10 vaccinates were protected from viremia following the second challenge, suggesting that vaccine-induced immunity to FIV persisted for at least 8 months. However, more stringent analysis for evidence of infection revealed that 5 of 10 vaccinates harbored virus in lymphoid tissues. Unlike the protection observed immediately following vaccination, which correlated positively with virus neutralizing antibody titer, the ability to resist a second challenge with FIV was more closely correlated with the induction of Env-specific cytotoxic T-cell activity. The results indicate that both virus-specific humoral immunity and cellular immunity play a role in the protection induced in cats by WIV immunization but their relative importance may be dependent on the interval between vaccination and exposure to virus.

Env-specific CTL predominate in cats protected from feline immunodeficiency virus infection by vaccination.

Animal models of HIV-1 have a key role to play in elucidation of the cellular mechanisms responsible for protective immunity. Vaccination of domestic cats with whole inactivated feline immunodeficiency virus (FIV) elicits virus-neutralizing Abs and virus-specific CTL in the peripheral blood and lymphoid organs and affords protection from homologous virus challenge. In the present study we confirm the induction of virus-specific CTL following immunization with whole inactivated FIV vaccine and demonstrate that cats are protected for up to 1 yr following vaccination. Long term protection in vaccinated cats correlates with both higher levels of FIV Env-specific CTL in the peripheral blood following vaccination and the presence of FIV Env-specific memory CD8+ CTL in the lymph nodes, which persist for up to 1 yr following challenge in the absence of detectable virus. The CTL responses observed in vaccinated protected cats differ qualitatively from those in FIV-infected cats. The latter cats either do not generate a memory CTL response or exhibit a Gag-specific memory CTL response. These results show that the protective immunity observed in whole inactivated virus-vaccinated cats is associated with the induction of high levels of Env-specific CTL activity.

FIV vaccine studies. I. Immune response to recombinant FIV env gene products and outcome after challenge infection

We have vaccinated five groups of cats ( n = 25) four times with five preparations of recombinant feline immunodeficiency virus (FIV) env gene products; one group ( n = 7) served as control. The vaccine formulations were as follows: (1) envelope glycoprotein of FIV Zurich 2 (FIV Z2) expressed in a Baculovirus system and isolated by gel electroelution (denatured form); (2) insect cells expressing FIV Z2 glycoprotein; (3) envelope glycoprotein of a Boston strain (FIV Bangston) expressed in insect cells and isolated by gel electroelution (denatured form); (4) glycosylated Bangston envelope protein made in insect cells and isolated in a native form; (5) non-glycosylated Bangston envelope protein made in Escherichia coli. All cats were challenged with 20 50% cat infective doses (CID 50) of FIV Z2 previously titrated in cats. All vaccinated cats developed high enzyme-linked immunosorbent assay (ELISA) antibodies to the homologous antigen; crossreactivity to heterologous antigens was seen at a lower level. Virus neutralizing antibodies (tested with Petaluma virus) reached titers up to 32. After challenge, all cats seroconverted (as judged by anti gag antibodies in Western blot) and became infected (as judged by virus isolation and/or polymerase chain reaction) between 4 and 11 weeks with the exception of one cat. It is concluded that it is relatively easy to induce high ELISA antibody titers using recombinant env gene products, ELISA antibody titers do not correlate with virus neutralization or with protection.

FIV vaccine studies. II. Clinical findings, hematological changes and kinetics of blood lymphocyte subsets

Five groups of cats were vaccinated with different recombinant feline immunodeficiency virus (FIV) SU vaccines expressed either in Escherichia coli or in the Baculovirus system. In Part I of this series, we described the humoral immune response and outcome of intraperitoneal FIV challenge exposure. Additionally, all cats were monitored for clinical and hematological changes and the course of blood lymphocyte subsets. These results are described in this present paper. A great increase of antibodies was found after vaccination with different recombinant FIV antigens, which did not protect the cats from intraperitoneal FIV challenge infection. This observation was paralleled by an increase of eosinophils during vaccination which was even more pronounced after challenge infection. After FIV challenge, infection lymphadenopathy, gingivitis, pharyngitis, changes in total leukocytes and neutrophils and a decrease in the CD4 +:CD8 + ratio were found in cats of all groups and were considered as a sign of the FIV infection taking place, independent of vaccination. The following observations suggest that in these cats a T H2-like immune response was elicited: the high counts of eosinophils, the nature of antigen and adjuvant (aluminium hydroxide) and the high amounts of antigens used for immunization. Clearly, this type of immune response did not protect the animals from intraperitoneal FIV challenge infection.

Protection against homologous but not heterologous challenge induced by inactivated feline immunodeficiency virus vaccines.

Whole inactivated virus vaccines from the FL4 cell line protected against challenge with homologous feline immunodeficiency virus (Petaluma strain) but not against a heterologous FIV isolate (GL-8) which is distinct from the Petaluma strain in virus neutralization. Protection was associated with a type-specific neutralizing antibody response and was retained when the challenge virus was propagated in an unrelated cell line.

Identification of three feline immunodeficiency virus (FIV) env gene subtypes and comparison of the FIV and human immunodeficiency virus type 1 evolutionary patterns

Feline immunodeficiency virus (FIV) is a lentivirus associated with AIDS-like illnesses in cats. As such, FIV appears to be a feline analog of human immunodeficiency virus (HIV). A hallmark of HIV infection is the large degree of viral genetic diversity that can develop within an infected individual and the even greater and continually increasing level of diversity among virus isolates from different individuals. Our goal in this study was to determine patterns of FIV genetic diversity by focusing on a 684-nucleotide region encompassing variable regions V3, V4, and V5 of the FIV env gene in order to establish parallels and distinctions between FIV and HIV type 1 (HIV-1). Our data demonstrate that, like HIV-1, FIV can be separated into distinct envelope sequence subtypes (three are described here). Similar to that found for HIV-1, the pairwise sequence divergence within an FIV subtype ranged from 2.5 to 15.0%, whereas that between subtypes ranged from 17.8 to 26.2%. However, the high number of synonymous nucleotide changes among FIV V3 to V5 env sequences may also include a significant number of back mutations and suggests that the evolutionary distances among FIV subtypes are underestimated. Although only a few subtype B viruses were available for examination, the pattern of diversity between the FIV A and B subtypes was found to be significantly distinct; subtype B sequences had proportionally fewer mutations that changed amino acids, compared with silent changes, suggesting a more advanced state of adaptation to the host. No similar distinction was evident for HIV-1 subtypes. The diversity of FIV genomes within individual infected cats was found to be as high as 3.7% yet twofold lower than that within HIV-1-infected people over a comparable region of the env gene. Despite these differences, significant parallels between patterns of FIV evolution and HIV-1 evolution exist, indicating that a wide array of potentially divergent virus challenges need to be considered in FIV vaccine and pathogenesis studies.

FIV as a Model for AIDS Vaccination

AIDS Research and Human RetrovirusesVol. 10, No. 3 FIV as a Model for AIDS VaccinationCALVIN M. JOHNSON, BARBARA A. TORRES, HIROYUKI KOYAMA, and JANET K. YAMAMOTOCALVIN M. JOHNSONSearch for more papers by this author, BARBARA A. TORRESSearch for more papers by this author, HIROYUKI KOYAMASearch for more papers by this author, and JANET K. YAMAMOTOSearch for more papers by this authorPublished Online:16 Mar 2009https://doi.org/10.1089/aid.1994.10.225AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byPhylogenetic characterisation of naturally occurring feline immunodeficiency virus in the United KingdomVeterinary Microbiology, Vol. 150, No. 3-4Neutralization of feline immunodeficiency virus by antibodies targeting the V5 loop of Env23 September 2009 | Journal of General Virology, Vol. 91, No. 1Dual-subtype FIV vaccine (Fel-O-Vax® FIV) protection against a heterologous subtype B FIV isolate11 November 2016 | Journal of Feline Medicine and Surgery, Vol. 7, No. 1Pre-existing immunity to pathogenic Listeria monocytogenes does not prevent induction of immune responses to feline immunodeficiency virus by a novel recombinant Listeria monocytogenes vaccineVaccine, Vol. 23, No. 12Feline immunodeficiency virus subtypes A, B and C and intersubtype recombinants in Ontario, CanadaJournal of General Virology, Vol. 85, No. 7Hematopoiesis in the feline fetal liver: an assessment by flow cytometryVeterinary Immunology and Immunopathology, Vol. 99, No. 1-2Inhibition of feline immunodeficiency virus (FIV) replication by DNA binding polyamidesBioorganic & Medicinal Chemistry Letters, Vol. 12, No. 15Is AZT/3TC therapy effective against FIV infection or immunopathogenesis?Veterinary Immunology and Immunopathology, Vol. 85, No. 3-4Vaccination with Inactivated Virus but Not Viral DNA Reduces Virus Load following Challenge with a Heterologous and Virulent Isolate of Feline Immunodeficiency VirusJournal of Virology, Vol. 74, No. 20Protective Immunity against Feline Immunodeficiency Virus Induced by Inoculation with vif-Deleted Proviral DNAVirology, Vol. 273, No. 1MHC-Restricted Protection of Cats against FIV Infection by Adoptive Transfer of Immune Cells from FIV-Vaccinated DonorsCellular Immunology, Vol. 198, No. 1Efficacy evaluation of prime–boost protocolAIDS, Vol. 12, No. 1Effect of dual-subtype vaccine against feline immunodeficiency virus infectionVeterinary Microbiology, Vol. 58, No. 2-4Perspectives on FIV vaccine developmentVaccine, Vol. 15, No. 12-13Virus Neutralizing Antibody Titer to Feline Immunodeficiency Virus Isolates of Subtypes A, B and D in Experimentally or Naturally Infected Cats.Journal of Veterinary Medical Science, Vol. 59, No. 5Feline immunodeficiency virus vaccination: characterization of the immune correlates of protectionJournal of Virology, Vol. 70, No. 11Immunohistochemical demonstration of cellular antigens of the cat defined by anti-human antibodiesVeterinary Immunology and Immunopathology, Vol. 53, No. 1-2Suppression of virus burden by immunization with feline immunodeficiency virus Env proteinVaccine, Vol. 14, No. 5Involvement of gag- and env-Specific Cytotoxic T Lymphocytes in Protective Immunity to Feline Immunodeficiency Virus J.N. FLYNN, J.A. BEATTY, C.A. CANNON, E.B. STEPHENS, M.J. HOSIE, J.C. NEIL, and O. JARRETT16 March 2009 | AIDS Research and Human Retroviruses, Vol. 11, No. 9Feline Immunodeficiency Virus as a Vaccine ModelVaccines against RetrovirusesSuperinfection of Cats with Feline Immunodeficiency Virus Subtypes A and B SUSUMU OKADA, RUIYU PU, ELI YOUNG, WILLIAM V. STOFFS, and JANET K. YAMAMOTO16 March 2009 | AIDS Research and Human Retroviruses, Vol. 10, No. 12 Volume 10Issue 3Mar 1994 To cite this article:CALVIN M. JOHNSON, BARBARA A. TORRES, HIROYUKI KOYAMA, and JANET K. YAMAMOTO.FIV as a Model for AIDS Vaccination.AIDS Research and Human Retroviruses.Mar 1994.225-228.http://doi.org/10.1089/aid.1994.10.225Published in Volume: 10 Issue 3: March 16, 2009PDF download

Current Thoughts on Feline Immunodeficiency Virus Infection

The feline immunodeficiency virus (FIV) is a novel feline retrovirus of the lentivirus subfamily that is known to induce immunodeficiency disorders in experimentally and naturally infected cats. Recent studies have characterized the stages of infection and specific immune deficits associated with FIV infection. Host cell populations harboring the virus have been better elucidated. Molecular cloning and nucleotide sequence analysis of the genomes of several isolates of FIV indicate sequence variation in the env gene of FIV, as has been found with other lentiviruses. Sequence of the genome has allowed the development of molecular reagents, including FIV DNA probes, polymerase chain reaction primers, and recombinant viral proteins, which have been and will be useful for FIV diagnostics and for pathogenesis studies. Investigations characterizing FIV as an animal model for human AIDS has yielded significant information concerning FIV infection in naturally infected cats and also may yield FIV vaccines and antiviral therapeutics useful for the pet cat population.

Enhancement after feline immunodeficiency virus vaccination

Cats were vaccinated with one of the three preparations: purified feline immunodeficiency virus (FIV) incorporated into immune stimulating complexes (ISCOMs), recombinant FIV p24 ISCOMs, or a fixed, inactivated cell vaccine in quil A. Cats inoculated with the FIV ISCOMs or the recombinant p24 ISCOMs developed high titres of antibodies against the core protein p24 but had no detectable antibodies against the env protein gp120 or virus neutralising antibodies. In contrast, all of the cats inoculated with the fixed, inactivated cell vaccine developed anti-env antibodies and four of five had detectable levels of neutralising antibody. However, none of the vaccinated cats were protected from infection after intraperitoneal challenge with 20 infectious units of FIV. Indeed there appeared to be enhancement of infection after vaccination as the vaccinated cats become viraemic sooner than the unvaccinated controls, and 100% of the vaccinated cats became viraemic compared with 78% of the controls. The mechanism responsible for this enhancement remains unknown.

Experimental vaccine protection against feline immunodeficiency virus.

Infection of domestic cats with the feline immunodeficiency virus (FIV) represents an important veterinary health problem and a useful animal model for the development of vaccines against acquired immunodeficiency syndrome (AIDS). Two experimental FIV vaccines have been developed; one consisting of fixed infected cells (Vaccine 1), the other of inactivated whole virus (Vaccine 2). After 4-6 immunizations over 2-5 months, both vaccines induced a strong FIV-specific immune response including neutralizing antibody and T-cell proliferation. Vaccine 1 protected 6 of 9 and Vaccine 2 protected 5 of 6 recipient cats against any detectable infection with a low dose (10 animal ID50) of FIV given intraperitoneally 2 weeks after the final boost. One additional cat in each vaccine group had a transient infection at 5-7 weeks postchallenge following which virus could no longer be detected. Thus, a total of 13 of 15 vaccinated cats were protected against persistent infection. By contrast, 13 of 13 controls were persistently infected by this challenge. The infected cell vaccine failed to protect against a higher dose (5 x 10(4) ID50) of FIV. These results indicate that vaccine prophylaxis against natural FIV infection should be achievable and enhance optimism of the prospect of developing an effective AIDS vaccine for humans.