Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 17, Pages 7131-7136Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1103869108
Keywords
viral vector; Pox virus
Categories
Funding
- National Institute of Allergy and Infectious Diseases [AI081677, AI08177-01A1S1]
- Bill and Melinda Gates Foundation
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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 mu g of both HIV Gag p24 vaccines elicited potent CD4(+) T cells secreting IL-2, IFN-gamma, and TNF-alpha, 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 similar to 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.
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