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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.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2011 Apr 26; Vol. 108 (17), pp. 7131-6. Date of Electronic Publication: 2011 Apr 05. - Publication Year :
- 2011
-
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.
- Subjects :
- AIDS Vaccines genetics
AIDS Vaccines pharmacology
Animals
B-Lymphocytes immunology
Cytokines immunology
Female
HIV Antibodies immunology
HIV Core Protein p24 pharmacology
Immunity, Cellular drug effects
Immunity, Cellular genetics
Immunity, Cellular immunology
Macaca mulatta
Male
RNA, Double-Stranded immunology
Vaccinia virus genetics
AIDS Vaccines immunology
Adjuvants, Immunologic pharmacology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
HIV Core Protein p24 immunology
RNA, Double-Stranded pharmacology
Vaccinia virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 108
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 21467219
- Full Text :
- https://doi.org/10.1073/pnas.1103869108