Grant: Operating Grant

Current HIV vaccine strategies utilize one or several proteins as immunogens. Studies showed that such strategies might not be the best approach because the epitopes are not equal in inducing protective immune responses and some might increase the susceptibility to HIV-1 infection. Therefore, the components to be included in the vaccines should be selective. Since HIV depends on host to survival, the interactions between virus and the host immune system can provide a clue to which immunogenes should be included in an HIV vaccine candidate. The error prone reverse transcriptase of HIV-1 generates a diversity of variants called quasispecies. Host T cell responses influence and select viral mutations. The viral variants escaping host immune responses have been defined as positively selected (PS) mutations. The effect of PS mutations are not equal, some PS mutations allow the virus to survive at a fitness cost. Identification and study of these PS mutations may locate regions of the viral genome that could potentially be included in vaccine candidates. Human Leukocyte antigens (HLA) are a group of proteins responsible for detecting infectious pathogens. PS mutations reflect viral escape from host immune responses in the context of HLA restricted CD8+ T cell responses. Identifying epitopes by correlating PS mutations in HIV-1 with specific host HLA alleles has certain advantages. The epitopes identified are immunologically relevant due to the fact that they are under immune pressure. However, the specific epitopes within these regions must be confirmed and characterized by direct biological assays. Our pilot study showed that characterizing the HIV epitopes under host selection can provide critical insight in identifying vulnerable regions of the virus and the targets for candidate vaccines. The study will identify and characterize the immunologically relevant HIV epitopes that can be included in a T cell based vaccine.