T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge

Mauricio A. Martins, Nancy A. Wilson, Jason S. Reed, Chanook D. Ahn, Yann C. Klimentidis, David B. Allison, David I. Watkins

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Determining the "correlates of protection" is one of the challenges in human immunodeficiency virus vaccine design. To date, T-cell-based AIDS vaccines have been evaluated with validated techniques that measure the number of CD8+ T cells in the blood that secrete cytokines, mainly gamma interferon (IFN-γ), in response to synthetic peptides. Despite providing accurate and reproducible measurements of immunogenicity, these methods do not directly assess antiviral function and thus may not identify protective CD8+ T-cell responses. To better understand the correlates of vaccine efficacy, we analyzed the immune responses elicited by a successful T-cell-based vaccine against a heterologous simian immunodeficiency virus challenge. We searched for correlates of protection using a viral suppression assay (VSA) and an IFN-γ enzyme-linked immunospot assay. While the VSA measured in vitro suppression, it did not predict the outcome of the vaccine trial. However, we found several aspects of the vaccine-induced T-cell response that were associated with improved outcome after challenge. Of note, broad vaccine-induced prechallenge T-cell responses directed against Gag and Vif correlated with lower viral loads and higher CD4+ lymphocyte counts. These results may be relevant for the development of T-cell-based AIDS vaccines since they indicate that broad epitope-specific repertoires elicited by vaccination might serve as a correlate of vaccine efficacy. Furthermore, the present study demonstrates that certain viral proteins may be more effective than others as vaccine immunogens.

Original languageEnglish (US)
Pages (from-to)4352-4365
Number of pages14
JournalJournal of virology
Volume84
Issue number9
DOIs
StatePublished - May 2010
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge'. Together they form a unique fingerprint.

Cite this