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

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

Content Provider	Scilit
Author	Flamar, Anne-Laure Xue, Yaming Zurawski, Sandra M. Montes, Monica King, Bryan Sloan, Louis Oh, Sang Kon Banchereau, Jacques Levy, Yves Zurawski, Gerard
Copyright Year	2013
Description	Journal: Aids 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.
Related Links	http://europepmc.org/articles/pmc3859846?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859846/pdf
Ending Page	2051
Page Count	11
Starting Page	2041
ISSN	02699370
e-ISSN	14735571
DOI	10.1097/qad.0b013e3283624305
Journal	Aids
Issue Number	13
Volume Number	27
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publisher Date	2013-08-24
Access Restriction	Open
Subject Keyword	Journal: Aids Dendritic Cell T Cell
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Immunology and Allergy Immunology

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

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