Prototype and commercial dual-subtype FIV vaccines, consisting of inactivated subtype-A and -D strains, conferred sterilizing protection against homologous subtype, subtype-A/B recombinant, and heterologous subtype-B challenges. The mechanisms of dual-subtype FIV vaccine protection in cats should provide insights to the development of effective HIV-1/AIDS vaccine in humans. Passive antibody immunization with purified dual-subtype FIV vaccine-induced immunoglobulin to na?ve cats afforded protection of the recipient cats against homologous subtype, which correlated with the presence of vaccine-induced virus neutralizing antibodies (VNA). In contrast, passive protection was not achieved against heterologous subtype-B challenge with VNA-resistant strain. Moreover, adoptive transfer (A-T) of T-cell enriched population from vaccinated cats to MHC-matched cats protected the A-T recipient against homologous and heterologous challenges. Dual-subtype vaccination using combined immunization routes (subcutaneous, intradermal, transcutaneous, &intranasal) afforded protection against homologous vaginal challenge. These results from the previous funding cycle suggest that protection against vaccine-induced VNA-susceptible strains (homologous subtype strains) is mediated by both VNA immunity and cell-mediated immunity (CMI), while vaccine protection against heterologous subtype strains is mediated by CMI. The studies in the competitive renewal grant are aimed at identifying the phenotypes and functions of the T cells as well as the viral epitopes and MHC profiles responsible for the dual-subtype vaccine protection (Specific aim 1). The proposed studies will also identify the best vaccination route(s) and the mechanisms of vaccine protection against mucosal-vaginal challenges with heterologous strains from homologous or heterologous subtype (Specific aim 2). The ultimate goal of these studies is to provide insights about which viral components, host immune responses, MHC profiles, and vaccination routes are important for an effective prophylaxis against the predominant transmission modes (mucosal and intravenous) of HIV-1 in humans. PROJECT NARRATIVE Over 1.8 million doses of commercial feline immunodeficiency virus (FIV) vaccine have been sold since July 2002 without any cases of vaccine failure. FIV causes feline AIDS in pet cats and has worldwide prevalence similar to HIV-1. The mechanisms of this FIV vaccine protection and viral proteins important for such protection will be determined in the proposed studies of this grant. Findings from these studies should advance our understanding about how to design an effective HIV-1 vaccine in humans.
| Aranyos, Alek M; Roff, Shannon R; Pu, Ruiyu et al. (2016) An initial examination of the potential role of T-cell immunity in protection against feline immunodeficiency virus (FIV) infection. Vaccine 34:1480-8 |
| Roff, Shannon R; Sanou, Missa P; Rathore, Mobeen H et al. (2015) Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects. Hum Vaccin Immunother 11:1540-56 |
| Coleman, James K; Pu, Ruiyu; Martin, Marcus M et al. (2014) Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies. Vaccine 32:746-54 |
| Roff, Shannon R; Noon-Song, Ezra N; Yamamoto, Janet K (2014) The Significance of Interferon-? in HIV-1 Pathogenesis, Therapy, and Prophylaxis. Front Immunol 4:498 |
| Sanou, Missa P; Roff, Shannon R; Mennella, Antony et al. (2013) Evolutionarily conserved epitopes on human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus reverse transcriptases detected by HIV-1-infected subjects. J Virol 87:10004-15 |
| Abbott, Jeffrey R; Pu, Ruiyu; Coleman, James K et al. (2012) Utilization of feline ELISPOT for mapping vaccine epitopes. Methods Mol Biol 792:47-63 |
| Sanou, Missa P; De Groot, Anne S; Murphey-Corb, Michael et al. (2012) HIV-1 Vaccine Trials: Evolving Concepts and Designs. Open AIDS J 6:274-88 |
| Abbott, J R; Sanou, M P; Coleman, J K et al. (2011) Evolutionarily conserved T-cell epitopes on FIV for designing an HIV/AIDS vaccine. Vet Immunol Immunopathol 143:246-54 |
| Yamamoto, Janet K; Sanou, Missa P; Abbott, Jeffrey R et al. (2010) Feline immunodeficiency virus model for designing HIV/AIDS vaccines. Curr HIV Res 8:14-25 |
| Uhl, Elizabeth W; Martin, Marcus; Coleman, James K et al. (2008) Advances in FIV vaccine technology. Vet Immunol Immunopathol 123:65-80 |
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