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Journal of Virology, October 2001, p. 9210-9228, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9210-9228.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of Human Immunodeficiency Virus Type 1 Subtype C Gag-, Tat-, Rev-, and Nef-Specific Elispot-Based Cytotoxic T-Lymphocyte Responses for AIDS Vaccine Design

V. Novitsky,1 N. Rybak,1 M. F. McLane,1 P. Gilbert,1 P. Chigwedere,1 I. Klein,1 S. Gaolekwe,2 S. Y. Chang,1 T. Peter,3 I. Thior,3 T. Ndung'u,1 F. Vannberg,4 B. T. Foley,5 R. Marlink,1 T. H. Lee,1 and M. Essex1,*

Harvard School of Public Health1 and Harvard Medical School,4 Boston, Massachusetts; National Health Laboratory/National Blood Transfusion Center2 and Botswana-Harvard Partnership for HIV Research and Education,3 Gaborone, Botswana; and Theoretical Biology and Biophysics, Group T-10, Los Alamos National Laboratory, Los Alamos, New Mexico5

Received 10 May 2001/Accepted 25 June 2001

The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occurring in southern Africa. It is caused by HIV-1 subtype C (HIV-1C). In this study we present the identification and analysis of cumulative cytotoxic T-lymphocyte (CTL) responses in the southern African country of Botswana. CTLs were shown to be an important component of the immune response to control HIV-1 infection. The definition of optimal and dominant epitopes across the HIV-1C genome that are targeted by CTL is critical for vaccine design. The characteristics of the predominant virus that causes the HIV-1 epidemic in a certain geographic area and also the genetic background of the population, through the distribution of common HLA class I alleles, might impact dominant CTL responses in the vaccinee and in the general population. The enzyme-linked immunospot (Elispot) gamma interferon assay has recently been shown to be a reliable tool to map optimal CTL epitopes, correlating well with other methods, such as intracellular staining, tetramer staining, and the classical chromium release assay. Using Elispot with overlapping synthetic peptides across Gag, Tat, Rev, and Nef, we analyzed HIV-1C-specific CTL responses of HIV-1-infected blood donors. Profiles of cumulative Elispot-based CTL responses combined with diversity and sequence consensus data provide an additional characterization of immunodominant regions across the HIV-1C genome. Results of the study suggest that the construction of a poly-epitope subtype-specific HIV-1 vaccine that includes multiple copies of immunodominant CTL epitopes across the viral genome, derived from predominant HIV-1 viruses, might be a logical approach to the design of a vaccine against AIDS.

* Corresponding author. Mailing address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, FXB-402, 651 Huntington Ave., Boston, MA 02115. Phone: (617) 432-0975. Fax: (617) 739-8348. E-mail: messex{at}hsph.harvard.edu.

Journal of Virology, October 2001, p. 9210-9228, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9210-9228.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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