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 journalArticle

36 Citations (Scopus)

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

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Vaccines
T-lymphocytes
vaccines
T-Lymphocytes
AIDS Vaccines
Enzyme-Linked Immunospot Assay
assays
immune response
Viral Proteins
CD4 Lymphocyte Count
Viral Load
Interferons
synthetic peptides
Interferon-gamma
viral proteins
lymphocyte count
Antiviral Agents
Human immunodeficiency virus

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Martins, M. A., Wilson, N. A., Reed, J. S., Ahn, C. D., Klimentidis, Y. C., Allison, D. B., & Watkins, D. I. (2010). T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge. Journal of Virology, 84(9), 4352-4365. https://doi.org/10.1128/JVI.02365-09

T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge. / Martins, Mauricio A.; Wilson, Nancy A.; Reed, Jason S.; Ahn, Chanook D.; Klimentidis, Yann C; Allison, David B.; Watkins, David I.

In: Journal of Virology, Vol. 84, No. 9, 05.2010, p. 4352-4365.

Research output: Contribution to journalArticle

Martins, Mauricio A. ; Wilson, Nancy A. ; Reed, Jason S. ; Ahn, Chanook D. ; Klimentidis, Yann C ; Allison, David B. ; Watkins, David I. / T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge. In: Journal of Virology. 2010 ; Vol. 84, No. 9. pp. 4352-4365.
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