Recent discovery in our laboratory revealed that 77-78% of specific-pathogen-free (SPF) cats immunized with clade B HIV-1/UCD1 vaccine were protected against subsequent FIV infection. Based on sequence analysis of HIV-1/UCD1 and FIV p24 proteins, a significant protection rate was achieved against FIV infection with a vaccine consisting of only HIV-1 p24 protein whose sequence was so distinctly different from the challenge virus. HIV-1 p24 vaccines were more effective than FIV p24 vaccines derived from pathogenic FIV strains. In fact, enhancement of FIV challenge infection was observed in the FIV p24-vaccinated cats. These findings suggest that selection of HIV-1 immunogen is essential to the development of an effective HIV-1 vaccine.
Two specific aims are proposed to identify cross-protective HIV-1 p24 epitopes that may be useful as HIV-1 vaccine immunogens for humans. ? ? Specific Aim 1 will identify the cross-protective epitope(s) on HIV-1 clade B p24 using HIV/FIV-cat model and characterize the immunity induced by the protective epitopes.
Specific Aim 2 will determine the relevance of the conserved protective epitopes identified in the HIV/FIV-cat model to HIV-1 vaccine development of humans. Studies will be performed to determine the HIV-1 p24 epitopes recognized by PBMC from both HIV-1-positive individuals and HIV-1 p24-vaccinated cats, understand the molecular basis of such common recognition, and evaluate if such peptides are important for eliciting vaccine protection against FIV and against SIV as a model for future human vaccine studies. These studies are the first steps toward identifying conserved protective epitopes that can prevent HIV-1 infection of humans. The innovation of the proposed studies lies in the use of the HIV/FIV-cat model to identify the cross-protective epitopes that can be used as part of HIV-1 vaccine. ? ? ?
| Sahay, Bikash; Nguyen, Cuong Q; Yamamoto, Janet K (2017) Conserved HIV Epitopes for an Effective HIV Vaccine. J Clin Cell Immunol 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 |
| 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 |
| Yamamoto, Janet K; Pu, Ruiyu; Sato, Eiji et al. (2007) Feline immunodeficiency virus pathogenesis and development of a dual-subtype feline-immunodeficiency-virus vaccine. AIDS 21:547-63 |
