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Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates

Authors
 Barbara J. Flynn  ;  Kathrin Kastenmüller  ;  Ulrike Wille-Reece  ;  Georgia D. Tomaras  ;  Munir Alam  ;  Ross W. Lindsay  ;  Andres M. Salazar  ;  Beatriz Perdiguero  ;  Carmen E. Gomez  ;  Ralf Wagner  ;  Mariano Esteban  ;  Chae G. Park  ;  Christine Trumpfheller  ;  Tibor Keler  ;  Giuseppe Pantaleo  ;  Ralph M. Steinman  ;  Robert Seder 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.108(17) : 7131-7136, 2011 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2011
MeSH
AIDS Vaccines/genetics ; AIDS Vaccines/immunology* ; AIDS Vaccines/pharmacology ; Adjuvants, Immunologic/pharmacology* ; Animals ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Cytokines/immunology ; Female ; HIV Antibodies/immunology ; HIV Core Protein p24/immunology* ; HIV Core Protein p24/pharmacology ; Immunity, Cellular/drug effects ; Immunity, Cellular/genetics ; Immunity, Cellular/immunology ; Macaca mulatta ; Male ; RNA, Double-Stranded/immunology ; RNA, Double-Stranded/pharmacology* ; Vaccinia virus/genetics ; Vaccinia virus/immunology*
Keywords
viral vector ; Pox virus
Abstract
Protein vaccines, if rendered immunogenic, would facilitate vaccine development against HIV and other pathogens. We compared in nonhuman primates (NHPs) immune responses to HIV Gag p24 within 3G9 antibody to DEC205 ("DEC-HIV Gag p24"), an uptake receptor on dendritic cells, to nontargeted protein, with or without poly ICLC, a synthetic double stranded RNA, as adjuvant. Priming s.c. with 60 μg of both HIV Gag p24 vaccines elicited potent CD4(+) T cells secreting IL-2, IFN-γ, and TNF-α, which also proliferated. The responses increased with each of three immunizations and recognized multiple Gag peptides. DEC-HIV Gag p24 showed better cross-priming for CD8(+) T cells, whereas the avidity of anti-Gag antibodies was ∼10-fold higher with nontargeted Gag 24 protein. For both protein vaccines, poly ICLC was essential for T- and B-cell immunity. To determine whether adaptive responses could be further enhanced, animals were boosted with New York vaccinia virus (NYVAC)-HIV Gag/Pol/Nef. Gag-specific CD4(+) and CD8(+) T-cell responses increased markedly after priming with both protein vaccines and poly ICLC. These data reveal qualitative differences in antibody and T-cell responses to DEC-HIV Gag p24 and Gag p24 protein and show that prime boost with protein and adjuvant followed by NYVAC elicits potent cellular immunity.
Files in This Item:
T201194240.pdf Download
DOI
10.1073/pnas.1103869108
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95415
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