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.
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
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.
Correspondence to Gerard Zurawski, PhD, Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, Texas, 75204, USA. Tel: +1 214 557 9089; fax: +1 214 820 4813; e-mail: firstname.lastname@example.org
Received 26 August, 2012
Revised 21 February, 2013
Accepted 11 April, 2013
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).