Targeting concatenated HIV antigens to human CD40 expands a broad repertoire of multifunctional CD4+ and CD8+ T cells

Anne Laure Flamar, Yaming Xue, Sandra M. Zurawski, Monica Montes, Bryan King, Louis Sloan, Sangkon Oh, Jacques Banchereau, Yves Levy, Gerard Zurawski

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Objective: Targeting HIV antigens directly to dendritic cells using monoclonal antibodies against cell-surface receptors has been shown to evoke potent cellular immunity in animal models. The objective of this study was to configure an anti-human CD40 antibody fused to a string of five highly conserved CD4+ and CD8+ T-cell epitope-rich regions of HIV-1 Gag, Nef and Pol (αCD40.HIV5pep), and then to demonstrate the capacity of this candidate therapeutic vaccine to target these HIV peptide antigens to human dendritic cells to expand functional HIV-specific T cells. Methods: Antigen-specific cytokine production using intracellular flow cytometry and multiplex bead-based assay, and suppression of viral inhibition, were used to characterize the T cells expanded by αCD40.HIV5pep from HIV-infected patient peripheral blood mononuclear cell (PBMC) and dendritic cell/T-cell co-cultures. Results: This candidate vaccine expands memory CD4+ and CD8+ T cells specific to multiple epitopes within all five peptide regions across a wide range of major histocompatibility complex (MHC) haplotypes from HIV-infected patient PBMC and dendritic cell/T-cell co-cultures. These in vitro expanded HIV antigen-specific CD4+ and CD8+ T cells produce multiple cytokines and chemokines. αCD40.HIV5pepexpanded CD8 + T cells have characteristics of cytotoxic effector cells and are able to kill autologous target cells and suppress HIV-1 replication in vitro. Conclusion: Our data demonstrate the therapeutic potential of this CD40-targeting HIV candidate vaccine in inducing a broad repertoire of multifunctional T cells in patients.

Original languageEnglish (US)
Pages (from-to)2041-2051
Number of pages11
JournalAIDS
Volume27
Issue number13
DOIs
StatePublished - Aug 24 2013

Keywords

  • CD40
  • Dendritic cell
  • HIV
  • T cell
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Flamar, A. L., Xue, Y., Zurawski, S. M., Montes, M., King, B., Sloan, L., Oh, S., Banchereau, J., Levy, Y., & Zurawski, G. (2013). Targeting concatenated HIV antigens to human CD40 expands a broad repertoire of multifunctional CD4+ and CD8+ T cells. AIDS, 27(13), 2041-2051. https://doi.org/10.1097/QAD.0b013e3283624305