Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination

Academic Article

Abstract

  • Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8+ T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8+ T cells capable of this activity are clearly understood; consequently, little is known regarding the ability of vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined CD8+ T-cell subsets in combination with a highly standardized virus inhibition assay to evaluate CD8+ T-cell-mediated inhibition of viral replication. Here we show that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8+ T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes. As it did for chronically infected virus controllers, this activity correlated with HIV-1-specific CD107a or macrophage inflammatory protein 1β (MIP-1β) expression from HIV-1-specific T cells. Moreover, for vaccinees or virus controllers, purified memory CD8+ T cells from a wide range of differentiation stages were capable of significantly inhibiting virus replication. Our data define attributes of an antiviral CD8+ T-cell response that may be optimized in the search for an efficacious HIV-1 vaccine. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
  • Digital Object Identifier (doi)

    Author List

  • Freel SA; Lamoreaux L; Chattopadhyay PK; Saunders K; Zarkowsky D; Overman RG; Ochsenbauer C; Edmonds TG; Kappes JC; Cunningham CK
  • Start Page

  • 4998
  • End Page

  • 5006
  • Volume

  • 84
  • Issue

  • 10