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

J Infect Dis. 2005 May 1;191(9):1427-34. doi: 10.1086/428450. Epub 2005 Mar 30.


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.

Publication types

  • Clinical Conference
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Consensus Sequence
  • Cross Reactions
  • Female
  • Gene Products, nef / chemistry
  • Gene Products, nef / genetics
  • Geography
  • HIV Seropositivity / immunology*
  • HIV-1 / classification
  • HIV-1 / immunology*
  • Humans
  • Immunity, Cellular*
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • nef Gene Products, Human Immunodeficiency Virus


  • Gene Products, nef
  • nef Gene Products, Human Immunodeficiency Virus