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53 Predominant HIV-1C-Specific CTL Responses
V. Novitsky*1, N. Rybak1, M. F. McLane1, P. Gilbert1, P. Chigwedere1, I. Klein1, S. Gaolekwe2, S. Y. Chang1, T. Peter3, I. Thior3, T. Ndung’u1, F. Vannberg4, B. T. Foley5, R. Marlink1, T. H. Lee1, and M. Essex1
1HSPH, Boston, MA, USA; 2NHL, Gaborone, Botswana; 3BHP, Gaborone, Botswana; 4HMS, Boston, MA, USA; and 5LANL, Los Alamos, NM, USA
Background: A severe HIV-1 epidemic caused by HIV-1 subtype C (HIV-1C) occurs in Southern Africa. Although HIV-1-specific CTL responses are important components of the immune response in the course and control of HIV-1 infection, most CTL epitope studies performed have been based on HIV-1 subtype B and HLA types that are most often found in the Caucasian population. We addressed the identification and mapping of HIV-1C-specific CTL responses and their potential HLA class I restriction in Botswana, a Southern African country where the prevalence rate of HIV-1 infection is 35.8%.
Methods: HIV-1C-infected blood donors were chosen as study subjects. Near full-length genome sequencing and HLA class I typing were performed by standard molecular methods. INF-gamma-Elispot assay was applied to identify HIV-1C Gag-, Pol RT-, Vif-, Vpr-, Tat-, Rev-, Env gp41, and Nef-specific CTL responses using sets of overlapping subtype C-based synthetic peptides.
Results: Highly diversified HIV-1C in Botswana was characterized on the full-length genome level. Common HLA types and subtypes were determined among the study population. Clustering of predominant HIV-1C-specific Elispot-based CTL responses was identified across HIV-1C Gag, RT, Vif, Vpr, Tat, gp41, and Nef. No immunodominant regions were seen in the HIV-1C Rev. Defined CTL-rich regions were relatively conserved. The magnitude of CTL responses to HIV-1C-based peptides was higher than the magnitude of responses to HIV-1B-based peptides. Comparative analysis (normalized by amino acid diversity) demonstrated a relatively higher magnitude of HIV-1C Gag-specific responses.
Conclusions: We have identified and characterized profiles of predominant Elispot-based CTL responses across HIV-1C Gag, RT, Vif, Vpr, Tat, gp41, and Nef. Identified immunodominant regions might be considered in the vaccine design. Ranking of dominant and subdominant CTL responses in the context of predominant virus and common HLA types in a certain geographic area may be important for the design of an efficacious AIDS vaccine.
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