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

Juan García-Arriaza, Beatriz Perdiguero, Jonathan Heeney, Michael Seaman, David C. Montefiori, Celia Labranche, Nicole L. Yates, Xiaoying Shen, Georgia D. Tomaras, Guido Ferrari, Kathryn E. Foulds, Adrian McDermott, Shing Fen Kao, Mario Roederer, Natalie Hawkins, Steve Self, Jiansheng Yao, Patrick Farrell, Sanjay Phogat, Jim TartagliaSusan W. Barnett, Brian Burke, Anthony Cristillo, Deborah Weiss, Carter Lee, Karen Kibler, Bertram Jacobs, Benedikt Asbach, Ralf Wagner, Song Ding, Giuseppe Pantaleo, Mariano Esteban

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29 Scopus citations

Abstract

Wecompared 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 cladeCHIV-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 groupMconsensus, 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 orMuLVgp70-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 thatNYVACmay represent an alternative candidate to ALVAC in the development of a future HIV-1 vaccine.

Original languageEnglish (US)
Pages (from-to)8525-8539
Number of pages15
JournalJournal of virology
Volume89
Issue number16
DOIs
StatePublished - Jan 1 2015

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

García-Arriaza, J., Perdiguero, B., Heeney, J., Seaman, M., Montefiori, D. C., Labranche, C., Yates, N. L., Shen, X., Tomaras, G. D., Ferrari, G., Foulds, K. E., McDermott, A., Kao, S. F., Roederer, M., Hawkins, N., Self, S., Yao, J., Farrell, P., Phogat, S., ... Esteban, M. (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), 8525-8539. https://doi.org/10.1128/JVI.01265-15