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

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- y 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. [ABSTRACT FROM AUTHOR]