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 language | English (US) |
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Pages (from-to) | 2041-2051 |
Number of pages | 11 |
Journal | AIDS |
Volume | 27 |
Issue number | 13 |
DOIs | |
State | Published - Aug 24 2013 |
Keywords
- CD40
- Dendritic cell
- HIV
- T cell
- Vaccine
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases