AEGiS-14IAC: Characterization of HIV-1 gag and env specific responses in HIV-1 subtype C-infected individuals in India.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Characterization of HIV-1 gag and env specific responses in HIV-1 subtype C-infected individuals in India.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1183)

Thakar MR, Keating S, Bhonge LS, Lakhashe S, Rao AK, Bollinger RC, Paranjape RS
National AIDS Research Institute, Pune, India

BACKGROUND: Induction of CD8+ CTL responses is an important outcome for evaluation of candidate HIV-1 vaccines. Characterization of immunodominant epitopes in Indian subtype C viruses is crucial for the design of HIV vaccine strategy suitable for India and other regions with subtype C epidemic.

METHODS: Peripheral Blood Mononuclear cells from HIV-1 infected individuals (9 recently and 24 chronically infected) were screened for HIV-1 gag C and env B specific T cell responses by IFN-a ELISPOT assay using pools of overlapping peptides. The identification of immunodominant gag C epitopes based upon the common Indian HLA alleles was carried out in a subset of individuals, using a combination of peptide matrix and the computer-based algorithm;HLA Epitope Location Prophesier(HELP).

RESULTS: Six of 9 seroconverters showed responses to HIV-1 C gag while none responded to HIV- B env while from 24 HIV-1 seropositive individuals, 9 (38 %) and 18(75%) showed responses to HIV-1 C gag and HIV-1 B env respectively. 88% of env B responders showed clustered response to peptide stretch of amino acid (AA) positions 660 to 856 comprising of conserved gp41 region. The response to HIV-1 C gag was found to cluster between AA160 to AA290 in 5/6 seroconverters and 6/9 seropositives. Four immunodominant peptides were identified within this region using matrix technology in 4 individuals . The HELP revealed two previously reported epitopes with HLA-A2 and HLA-B35 restriction. In addition, five novel epitopes with HLA-B51, HLA-A2, HLA-B35 and HLA-Cw6 restriction were identified.

CONCLUSION: Seven HIV-1 subtype C gag epitopes were identified using combination of peptide matrix and computer based algorithm HELP. Two of four patients recognized multiple epitopes. Further characterization of the commonly identified immunodominant epitopes among the Indian patients may be important for selection and development of HIV-1 vaccine candidates for India

Keywords: AEGIS, HIV-1, AIDS Vaccines, HIV Infections, HLA-A2 Antigen, HIV Seropositivity, Epitopes, Immunodominant Epitopes, HLA-C Antigens, India, HLA-Cw6, Human, immunology

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TuOrA1183