More than half of the current HIV infections in the world are due to HIV-1 C, a genotype that deserves more thorough analysis. The most dramatic epidemic of HIV-1 C is currently expanding in countries such as Botswana. It has been estimated that 38.5 percent of all pregnant women, including almost half of the pregnant women between the age 20 and 29, in Botswana are infected. Because Botswana is a democratic country with a well organized health care system, it represents an ideal partner country for vaccine development efforts aimed at curbing the expanding HIV-1 epidemic in Southern Africa. The overall goal of this proposal is to test the hypothesis that, despite the unusually high degree of sequence divergence found in the HIV-1 subtype C viruses circulating in Botswana, conserved CTL epitopes that match the most common HLA types of Batswana (note: Botswana people are called Batswana) can be identified for HIV-1 C vaccine design. The first Specific Aim is to determine the frequency of the most common HLA types in Botswana. The methodology of genetic characterization will be adopted to achieve this objective. The second Specific Aim is the molecular characterization of HIV-1 C field isolates. The objective of this specific aim is to critically assess the extent of sequence divergence and to identify regions of high sequence homology. The last Specific Aim is to identify CTL epitopes located in the conserved regions of HIV-1 C genome. Particular emphasis will be placed on the identification of functional CTL epitopes that match the most common HLA types for Batswana. Most of the CTL epitopes identified thus far have been based largely on HIV-1 subtype B sequences and the HLA types of Caucasians. This proposed research would allow identification of HIV-1 CTL epitopes most relevant for the design of vaccines for at-risk populations in Southern Africa. Furthermore, the tetrameric complexes constructed for functional characterization of CTL epitopes would become valuable for monitoring post-immunization CTL responses in future HIV-1 vaccine trials.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-AARR-6 (01))
Program Officer
Pensiero, Michael N
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Schools of Public Health
United States
Zip Code
Boutwell, Christian L; Rowley, Christopher F; Essex, M (2009) Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein. J Virol 83:2460-8
Boutwell, Christian L; Essex, M (2007) Identification of HLA class I-associated amino acid polymorphisms in the HIV-1C proteome. AIDS Res Hum Retroviruses 23:165-74
Novitsky, Vladimir A; Gilbert, Peter B; Shea, Kimberly et al. (2006) Interactive association of proviral load and IFN-gamma-secreting T cell responses in HIV-1C infection. Virology 349:142-55
Gilbert, Peter B; Novitsky, Vladimir; Essex, Max (2005) Covariability of selected amino acid positions for HIV type 1 subtypes C and B. AIDS Res Hum Retroviruses 21:1016-30
Bussmann, Hermann; Novitsky, Vladimir; Wester, William et al. (2005) HIV-1 subtype C drug-resistance background among ARV-naive adults in Botswana. Antivir Chem Chemother 16:103-15
Bussmann, Hermann; Wester, C William; Masupu, Kereng V et al. (2004) Low CD4+ T-lymphocyte values in human immunodeficiency virus-negative adults in Botswana. Clin Diagn Lab Immunol 11:930-5
McKinney, Denise M; Skvoretz, Rhonda; Livingston, Brian D et al. (2004) Recognition of variant HIV-1 epitopes from diverse viral subtypes by vaccine-induced CTL. J Immunol 173:1941-50
Novitsky, V; Gilbert, P; Peter, T et al. (2003) Association between virus-specific T-cell responses and plasma viral load in human immunodeficiency virus type 1 subtype C infection. J Virol 77:882-90
Novitsky, V; Cao, H; Rybak, N et al. (2002) Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of immunodominant regions of human immunodeficiency virus type 1 subtype C. J Virol 76:10155-68
Novitsky, V; Smith, U R; Gilbert, P et al. (2002) Human immunodeficiency virus type 1 subtype C molecular phylogeny: consensus sequence for an AIDS vaccine design? J Virol 76:5435-51

Showing the most recent 10 out of 13 publications