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Increased detection of proliferating, polyfunctional, HIV-1-specific T cells in DNA-modified vaccinia virus Ankara-vaccinated human volunteers by cultured IFN-gamma ELISPOT assay.

Authors
Journal
European Journal of Immunology
0014-2980
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
39
Issue
4
Identifiers
DOI: 10.1002/eji.200839167
Keywords
  • Aids Vaccines
  • Amino Acid Sequence
  • Cd4-Positive T-Lymphocytes
  • Cd8-Positive T-Lymphocytes
  • Cell Culture Techniques
  • Cell Line
  • Cytokines
  • Hiv Antigens
  • Hiv-1
  • Humans
  • Immunologic Memory
  • Interferon-Gamma
  • Molecular Sequence Data
  • Peptides
  • Vaccines
  • Dna
Disciplines
  • Medicine

Abstract

Induction of a long-term immunological memory, which can expand and defend the host upon pathogen encounter, is the "holy grail" of vaccinology. Here, using a sensitive cultured IFN-gamma ELISPOT assay, we show that 50% (15 out of 30) of healthy, HIV-1/2-uninfected volunteers who received pTHr.HIVA DNA prime-modified vaccinia virus Ankara. HIVA boost vaccine regimen 1 to 3 1/2 years ago had detectable HIV-1-specific T-cell responses. These T cells, predominantly of the CD4(+) subtype, could proliferate and produce multiple cytokines in response to in vitro peptide stimulation. Peptide mapping studies showed that the vaccine-induced CD4(+) T cells were mostly directed toward epitopes targeted in HIV-1-infected individuals. In addition, we used the same assay to re-evaluate 51 volunteers from past vaccine trial IAVI-006 and corrected the previously reported 10% of vaccine responders to 50%. Thus, we confirmed that cultured assays are a valuable tool for studying T-cell memory. These results are discussed in the context of the current state-of-affairs of the HIV-1 vaccine field.

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