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1 May 2005

Volume 191, Number 9
The Journal of Infectious Diseases 2005;191:1427–1434
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19109-0008$15.00
DOI: 10.1086/428450
MAJOR ARTICLE

Cross‐Reactivity of Anti–HIV‐1 T Cell Immune Responses among the Major HIV‐1 Clades in HIV‐1–Positive Individuals from 4 Continents

Paul M. Coplan,1,a

Swati B. Gupta,1

Sheri A. Dubey,1

Punnee Pitisuttithum,2

Alex Nikas,1

Bernard Mbewe,3

Efthyia Vardas,7

Mauro Schechter,5

Esper G. Kallas,6

Dan C. Freed,1

Tong‐Ming Fu,1

Christopher T. Mast,1

Pilaipan Puthavathana,2

James Kublin,1

Kelly Brown Collins,1

John Chisi,3

Richard Pendame,4

Scott J. Thaler,1,b

Glenda Gray,7

James Mcintyre,7

Walter L. Straus,1

Jon H. Condra,1

Devan V. Mehrotra,1

Harry A. Guess,1,a

Emilio A. Emini,1,a and

John W. Shiver1

1Merck Research Laboratories, West Point, Pennsylvania; 2Mahidol University, Bangkok, Thailand; 3Malawi College of Medicine, Blantyre, and 4Ministry of Population and Health, Lilongwe, Malawi; 5Universidade Federal do Rio de Janeiro, Rio de Janeiro, and 6Federal University of São Paulo, São Paulo, Brazil; 7University of the Witwatersrand, Johannesburg, South Africa

Background.The genetic diversity of human immunodeficiency virus type 1 (HIV‐1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV‐1 clades. Therefore, we quantified the cross‐clade reactivity, among unvaccinated individuals, of anti–HIV‐1 T cell responses to the infecting HIV‐1 clade relative to other major circulating clades.

Methods.Cellular immune responses to HIV‐1 clades A, B, and C were compared by standardized interferon‐γ enzyme‐linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV‐1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross‐clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV‐1.

Results.Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross‐clade reactivity of cellular immune responses to HIV‐1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89–1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62–0.73]). The difference in cross‐clade reactivity to Nef and Gag proteins was significant ( ).

Conclusions.Cross‐clade reactivity of cellular immune responses can be substantial but varies by viral protein.

Received 1 May 2004; accepted 20 October 2004; electronically published 30 March 2005.

Reprints or correspondence: Dr. Paul Coplan, Executive Director of Clinical and Regulatory Affairs, International Partnership for Microbicides, 2997 Runnymede Dr., Plymouth Meeting, PA 19462 ().

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  • Presented in part: XIV International AIDS Conference, Barcelona, Spain, 7–12 July 2002 (abstract MoPeA3055).

    Potential conflicts of interest: Several coauthors are employees of Merck Research Laboratories. This study was funded by Merck Research Laboratories, the research division of Merck and Co., Inc; however, no product of Merck is evaluated in this research. This study was conducted as part of the early formative research for Merck’s HIV vaccine development program. P.M.C. was an employee of Merck at the time the data were collected for this study but currently is an employee of a nonprofit public‐private organization developing vaginal microbicides to prevent HIV infection and has no conflict of interest (no stock options, payment, or other incentive) in this research.

    Financial support: Merck Research Laboratories (research division of Merck and Co., Inc).

  • Present affiliations: University of North Carolina, Chapel Hill (H.A.G.); International AIDS Vaccine Initiative, New York, New York (E.A.E.); International Partnership for Microbicides, Silver Spring, Maryland (P.M.C.).

  • We note with sadness that one of the coauthors, Dr. Scott Thaler, recently passed away suddenly. Scott was kind, compassionate, a talented and outstanding researcher, and a pleasure to work with. We sorely miss him.

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