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AIDS. 2013 Aug 24;27(13):2041-51. doi: 10.1097/QAD.0b013e3283624305.

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

Author information

1
aBaylor Institute for Immunology Research, Dallas, Texas, USA bANRS HIV Vaccine Network/Vaccine Research Institute, Paris cEcole doctorale Sciences de la Vie et de la Santé, Université Paris-Est, Créteil, France dINSERM U899 eNorth Texas Infectious Diseases, Dallas, Texas, USA fUniversité Paris-Est, Faculté de Médecine, INSERM U955 gAssistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, service d'immunologie clinique, Créteil, France.

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.HIV5pep-expanded 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.

PMID:
23615121
PMCID:
PMC3859846
DOI:
10.1097/QAD.0b013e3283624305
[Indexed for MEDLINE]
Free PMC Article
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