Document Detail


Targeting concatenated HIV antigens to human CD40 expands a broad repertoire of multifunctional CD4+ and CD8+ T cells.
MedLine Citation:
PMID:  23615121     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anne-Laure Flamar; Yaming Xue; Sandra M Zurawski; Monica Montes; Bryan King; Louis Sloan; SangKon Oh; Jacques Banchereau; Yves Levy; Gerard Zurawski
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  27     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2014-01-06     Completed Date:  2014-07-03     Revised Date:  2014-08-27    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  2041-51     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
AIDS Vaccines / genetics,  immunology*
Antibodies, Monoclonal / immunology,  metabolism
Antigens, CD40 / immunology*,  metabolism
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology*
Cell Proliferation
Coculture Techniques
Dendritic Cells / immunology*
HIV Antigens / genetics,  immunology*,  metabolism
HIV-1 / genetics,  immunology*
Humans
Recombinant Fusion Proteins / genetics,  immunology,  metabolism
Grant Support
ID/Acronym/Agency:
U19 AI-57234/AI/NIAID NIH HHS; U19 AI057234/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/AIDS Vaccines; 0/Antibodies, Monoclonal; 0/Antigens, CD40; 0/HIV Antigens; 0/Recombinant Fusion Proteins
Comments/Corrections

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