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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.

Publication ,  Journal Article
García-Arriaza, J; Perdiguero, B; Heeney, J; Seaman, M; Montefiori, DC; Labranche, C; Yates, NL; Shen, X; Tomaras, GD; Ferrari, G; Foulds, KE ...
Published in: J Virol
August 2015

UNLABELLED: 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 C HIV-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 gp70-scaffolded V1/V2 were absent or very low in all immunization groups. Overall, these results provide a comprehensive survey of the immunogenicity of NYVAC versus 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.

Duke Scholars

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

August 2015

Volume

89

Issue

16

Start / End Page

8525 / 8539

Location

United States

Related Subject Headings

  • Virology
  • Viral Vaccines
  • Viral Plaque Assay
  • Vaccines, Synthetic
  • Promoter Regions, Genetic
  • Poxviridae
  • Macaca mulatta
  • HIV Infections
  • HIV Antigens
  • HIV Antibodies
 

Citation

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MLA
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García-Arriaza, J., Perdiguero, B., Heeney, J., Seaman, M., Montefiori, D. C., Labranche, C., … 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. J Virol, 89(16), 8525–8539. https://doi.org/10.1128/JVI.01265-15
García-Arriaza, Juan, Beatriz Perdiguero, Jonathan Heeney, Michael Seaman, David C. Montefiori, Celia Labranche, Nicole L. Yates, et al. “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.J Virol 89, no. 16 (August 2015): 8525–39. https://doi.org/10.1128/JVI.01265-15.
García-Arriaza J, Perdiguero B, Heeney J, Seaman M, Montefiori DC, Labranche C, et al. 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. J Virol. 2015 Aug;89(16):8525–39.
García-Arriaza, Juan, et al. “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.J Virol, vol. 89, no. 16, Aug. 2015, pp. 8525–39. Pubmed, doi:10.1128/JVI.01265-15.
García-Arriaza J, Perdiguero B, Heeney J, Seaman M, Montefiori DC, Labranche C, Yates NL, Shen X, Tomaras GD, Ferrari G, Foulds KE, McDermott A, Kao S-F, Roederer M, Hawkins N, Self S, Yao J, Farrell P, Phogat S, Tartaglia J, Barnett SW, Burke B, Cristillo A, Weiss D, Lee C, Kibler K, Jacobs B, Asbach B, Wagner R, Ding S, Pantaleo G, Esteban M. 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. J Virol. 2015 Aug;89(16):8525–8539.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

August 2015

Volume

89

Issue

16

Start / End Page

8525 / 8539

Location

United States

Related Subject Headings

  • Virology
  • Viral Vaccines
  • Viral Plaque Assay
  • Vaccines, Synthetic
  • Promoter Regions, Genetic
  • Poxviridae
  • Macaca mulatta
  • HIV Infections
  • HIV Antigens
  • HIV Antibodies