AEGiS-14IAC: Magnitude and frequency of CTL responses to HIV-1 subtype C.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Magnitude and frequency of CTL responses to HIV-1 subtype C.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1181)

Novitsky V, Rybak N, McLane MF, Gilbert P, Gaolekwe S, Peter T, Thior I, Ndung'u T, Marlink R, Lee TH, Essex M
Harvard School of Public Health, Boston, United States

BACKGROUND: An increasing dominance of subtype C in the AIDS epidemic reflects a dynamic alteration in the worldwide HIV-1 subtype distribution. The HIV-1C epicenter with the highest prevalence rate has evolved within the countries of southern Africa. CTL responses are an important component of the overall immune response to HIV infection. Knowledge of profiles of CTL responses within the HIV-1C epidemic might be a key factor in the design of an efficacious AIDS vaccine for southern Africa.

METHODS: HIV-1subtype C-specific CTL responses were analyzed in HIV-infected blood donors from Botswana by INF-gamma-Elispot assay. HIV-1 subtype C-specific synthetic peptides were designed based on the near full-length genome HIV-1C sequences. HLA class I typing was performed by sequencing and/or SSP.

RESULTS: Magnitude and frequency of HIV-1C-specific Elispot-based CTL responses were analyzed across all HIV-1C proteins. Immunodominant and subdominant regions within HIV-1C Gag p24, Pol RT, Vif, Vpr, Tat, Env gp120 and gp41, and Nef were identified. No immunodominant regions were found in the HIV-1C Pol PR, Rev or Vpu. Diversity within defined CTL-rich regions was lower as compared with the entire viral protein. The magnitude of CTL responses within HIV-1C Gag and Vpr were correlated with reduced plasma viral load, while CTL responses within HIV-1C Nef were correlated with increasing plasma viral load.

CONCLUSIONS: Profiles of Elispot-based CTL responses to the HIV-1C Gag, Pol, Vif, Vpr, Tat, Rev, Vpu, Env, and Nef were characterized by analyses of magnitude, frequency and cumulative CTL responses. Identified immunodominant and subdominant CTL-rich regions across the HIV-1C genome might exemplify targets for AIDS vaccine design. Including multiple copies of immunodominant regions in the vaccine constructs could potentially overcome high HIV-1C diversity and increase efficacy of a subtype C-specific vaccine.

Keywords: AEGIS, HIV-1, HIV Infections, AIDS Vaccines, Viral Load, Acquired Immunodeficiency Syndrome, Immunodominant Epitopes, Prevalence, HIV Seropositivity, Africa, Southern, Botswana, epidemiology, immunology

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TuOrA1181