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

Content Provider	PubMed Central
Author	Flynn, Barbara J. Kastenmüller, Kathrin Ulrike, Wille-reece Tomaras, Georgia D. Alam, Munir Lindsay, Ross W. Salazar, Andres M. Perdiguero, Beatriz Gomez, Carmen E. Wagner, Ralf Esteban, Mariano Park, Chae G. Christine, Trumpfheller Keler, Tibor Pantaleo, Giuseppe Steinman, Ralph M. Seder, Robert
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.
Related Links	http://dx.doi.org/10.1073/pnas.1103869108
Ending Page	7136
Page Count	6
Starting Page	7131
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	108
Language	English
Publisher	National Academy of Sciences
Publisher Date	2011-04-26
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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