Garcia-Arriaza, Juan and Perdiguero, Beatriz and Heeney, Jonathan and Seaman, Michael and Montefiori, David C. and Labranche, Celia and Yates, Nicole L. and Shen, Xiaoying and Tomaras, Georgia D. and Ferrari, Guido and Foulds, Kathryn E. and McDermott, Adrian and Kao, Shing-Fen and Roederer, Mario and Hawkins, Natalie and Self, Steve and Yao, Jiansheng and Farrell, Patrick and Phogat, Sanjay and Tartaglia, Jim and Barnett, Susan W. and Burke, Brian and Cristillo, Anthony and Weiss, Deborah and Lee, Carter and Kibler, Karen and Jacobs, Bert and Asbach, Benedikt and Wagner, Ralf and Ding, Song and Pantaleo, Giuseppe and Esteban, Mariano (2015) Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates. JOURNAL OF VIROLOGY, 89 (16). pp. 8525-8539. ISSN 0022-538X, 1098-5514
Full text not available from this repository. (Request a copy)Abstract
We compared the HIV-1-specific cellular and humoral immune responses elicited in rhesus macaques immunized with two poxvirus vectors (NYVAC and ALVAC) expressing the same HIV-1 antigens from clade C, Env gp140 as a trimeric cell-released protein and a Gag-Pol-Nef polyprotein as Gag-induced virus-like particles (VLPs) (referred to as NYVAC-C and ALVAC-C). The immunization protocol consisted of two doses of the corresponding poxvirus vector plus two doses of a combination of the poxvirus vector and a purified HIV-1 gp120 protein from clade C. This immunogenicity profile was also compared to that elicited by vaccine regimens consisting of two doses of the ALVAC vector expressing HIV-1 antigens from clades B/E (ALVAC-vCP1521) plus two doses of a combination of ALVAC-vCP1521 and HIV-1 gp120 protein from clades B/E (similar to the RV144 trial regimen) or clade C. The results showed that immunization of macaques with NYVAC-C stimulated at different times more potent HIV-1-specific CD4(+) T-cell responses and induced a trend toward higher-magnitude HIV-1-specific CD8(+) T-cell immune responses than did ALVAC-C. Furthermore, NYVAC-C induced a trend toward higher levels of binding IgG antibodies against clade CHIV-1 gp140, gp120, or murine leukemia virus (MuLV) gp70-scaffolded V1/V2 and toward best cross-clade-binding IgG responses against HIV-1 gp140 from clades A, B, and group M consensus, than did ALVAC-C. Of the linear binding IgG responses, most were directed against the V3 loop in all immunization groups. Additionally, NYVAC-C and ALVAC-C also induced similar levels of HIV-1-neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC) responses. Interestingly, binding IgA antibody levels against HIV-1 gp120 or MuLV gp 70-scaffolded V1/V2 were absent or very low in all immunization groups. Overall, these results provide a comprehensive survey of the immunogenicity of NYVACversus ALVAC expressing HIV-1 antigens in nonhuman primates and indicate that NYVAC may represent an alternative candidate to ALVAC in the development of a future HIV-1 vaccine. IMPORTANCE The finding of a safe and effective HIV/AIDS vaccine immunogen is one of the main research priorities. Here, we generated two poxvirus-based HIV vaccine candidates (NYVAC and ALVAC vectors) expressing the same clade C HIV-1 antigens in separate vectors, and we analyzed in nonhuman primates their immunogenicity profiles. The results showed that immunization with NYVAC-C induced a trend toward higher HIV-1-specific cellular and humoral immune responses than did ALVAC-C, indicating that this new NYVAC vector could be a novel optimized HIV/AIDS vaccine candidate for human clinical trials.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VACCINE EFFICACY TRIAL; B-CELL RESPONSES; PHASE-I TRIAL; VIRAL LOAD; DNA PRIME; VIRUS; MVA; CANDIDATES; NEUTRALIZATION; IMMUNIZATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Jul 2019 11:38 |
| Last Modified: | 03 Jul 2019 11:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5144 |
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