Abstract

BackgroundThe 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

MethodsCellular 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

ResultsCellular 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)

ConclusionsCross-clade reactivity of cellular immune responses can be substantial but varies by viral protein

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