Lessons from the RV144 Thai Phase III HIV-1 vaccine trial and the search for correlates of protection

Jerome H. Kim*, Jean Louis Excler, Nelson L. Michael

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

RV144 remains the only HIV-1 vaccine trial to demonstrate efficacy against HIV-1 acquisition. The prespecified analysis of immune correlates of risk showed that antibodies directed against the V1V2 region of gp120, in particular the IgG1 and IgG3 subclass mediating antibody-dependent cell-mediated cytotoxicity, seem to play a predominant role in protection against HIV-1 acquisition and that plasma envelope (Env)-specific IgA antibodies were directly correlated with risk. RV144 and recent nonhuman primate challenge studies suggest that Env is essential, and perhaps sufficient, to induce protective antibody responses against mucosal HIV-1 acquisition. Follow-up clinical trials are ongoing to further dissect the immune responses elicited by the RV144 ALVAC-HIV and AIDSVAX® B/E regimen. The study of gp120 Env immunogens and immune correlates of risk has resulted in the development of improved antigens. Whether the RV144 immune correlates of risk will generalize to other populations vaccinated with similar immunogens with different modes and intensity of transmission remains to be demonstrated. Efficacy trials are now planned in heterosexual populations in southern Africa and men who have sex with men in Thailand.

Original languageEnglish
Pages (from-to)423-427
Number of pages5
JournalAnnual Review of Medicine
Volume66
DOIs
StatePublished - 14 Jan 2015
Externally publishedYes

Keywords

  • HIV vaccine
  • antibody-dependent cytotoxicity
  • correlates of risk
  • efficacy
  • envelope
  • neutralizing antibody
  • nonneutralizing antibody

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