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

doi:10.1128/JVI.75.19.9210-9228.2001

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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-1subtype C (HIV-1C). In this study we present the identificationand analysis of cumulative cytotoxic T-lymphocyte (CTL) responsesin the southern African country of Botswana. CTLs were shown tobe an important component of the immune response to control HIV-1infection. The definition of optimal and dominant epitopes acrossthe HIV-1C genome that are targeted by CTL is critical for vaccinedesign. The characteristics of the predominant virus that causesthe HIV-1 epidemic in a certain geographic area and also the geneticbackground of the population, through the distribution of commonHLA class I alleles, might impact dominant CTL responses in thevaccinee and in the general population. The enzyme-linked immunospot(Elispot) gamma interferon assay has recently been shown to bea reliable tool to map optimal CTL epitopes, correlating wellwith other methods, such as intracellular staining, tetramer staining,and the classical chromium release assay. Using Elispot with overlappingsynthetic peptides across Gag, Tat, Rev, and Nef, we analyzedHIV-1C-specific CTL responses of HIV-1-infected blood donors.Profiles of cumulative Elispot-based CTL responses combined withdiversity and sequence consensus data provide an additional characterizationof immunodominant regions across the HIV-1C genome. Results ofthe study suggest that the construction of a poly-epitope subtype-specificHIV-1 vaccine that includes multiple copies of immunodominantCTL epitopes across the viral genome, derived from predominantHIV-1 viruses, might be a logical approach to the design of avaccine againstAIDS.

^* 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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