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Cross-reactivity of anti-HIV-1 T cell immune responses among the major HIV-1 clades in HIV-1-positive individuals from 4 continents.

Coplan PM, Gupta SB, Dubey SA, Pitisuttithum P, Nikas A, Mbewe B, Vardas E, Schechter M, Kallas EG, Freed DC, Fu TM, Mast CT, Puthavathana P, Kublin J, Brown Collins K, Chisi J, Pendame R, Thaler SJ, Gray G, Mcintyre J, Straus WL, Condra JH, Mehrotra DV, Guess HA, Emini EA, Shiver JW

Merck Research Laboratories, West Point, Pennsylvania, USA. pcoplan@ipm-microbicides.org

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- gamma 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 (P<.0001). CONCLUSIONS: Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.

Published 5 April 2005 in J Infect Dis, 191(9): 1427-34.
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