Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development

David Franco, Wenjing Li, Fang Qing, Cristina T. Stoyanov, Thomas Moran, Charles M. Rice, David D. Ho

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The failure to develop an effective vaccine against HIV-1 infection has led the research community to seek new ways of raising qualitatively different antibody and cellular immune responses. Towards this goal, we investigated the yellow fever 17D vaccine strain (YF17D), one of the most effective vaccines ever made, as a platform for HIV-1 vaccine development. A test antigen, HIV-1 p24 (clade B consensus), was inserted near the 5' end of YF17D, in frame and upstream of the polyprotein (YF-5'/p24), or between the envelope and the first non-structural protein (YF-E/p24/NS1). In vitro characterization of these recombinants indicated that the gene insert was more stable in the context of YF-E/p24/NS1. This was confirmed in immunogenicity studies in mice. CD8+ IFN-γ T-cell responses against p24 were elicited by the YF17D recombinants, as were specific CD4+ T cells expressing IFN-γ and IL-2. A balanced CD4+ and CD8+ T-cell response was notable, as was the polyfunctionality of the responding cells. Finally, the protective efficacy of the YF17D recombinants, particularly YF-E/p24/NS1, in mice challenged with a vaccinia expressing HIV-1 Gag was demonstrated. These results suggest that YF17D warrants serious consideration as a live-attenuated vector for HIV-1 vaccine development.

Original languageEnglish
Pages (from-to)5676-5685
Number of pages10
JournalVaccine
Volume28
Issue number35
DOIs
StatePublished - Aug 2010

Keywords

  • 17D
  • HIV-1
  • P24
  • Vaccine
  • Yellow fever virus

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