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

Flynn, Barbara J. and Kastenmueller, Kathrin and Wille-Reece, Ulrike and Tomaras, Georgia D. and Alam, Munir and Lindsay, Ross W. and Salazar, Andres M. and Perdiguero, Beatriz and Gomez, Carmen E. and Wagner, Ralf and Esteban, Mariano and Park, Chae G. and Trumpfheller, Christine and Keler, Tibor and Pantaleo, Giuseppe and Steinman, Ralph M. and Seder, Robert (2011) Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108 (17). pp. 7131-7136. ISSN 0027-8424,

Full text not available from this repository. (Request a copy)

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 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.

Item Type: Article
Uncontrolled Keywords: POLYRIBOINOSINIC-POLYRIBOCYTIDYLIC ACID; REPLICATION-DEFECTIVE ADENOVIRUS; PRIME-BOOST IMMUNIZATION; IN-VIVO; RHESUS MACAQUES; RESPONSES; ANTIBODY; DNA; CD4(+); VACCINATION; viral vector; Pox virus
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Jun 2020 06:34
Last Modified: 22 Jun 2020 06:34
URI: https://pred.uni-regensburg.de/id/eprint/20930

Actions (login required)

View Item View Item