Immunogenicity of NYVAC prime-protein boost HIV-1 envelope vaccination and SHIV challenge of nonhuman primates.
A preventive HIV-1 vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 viruses can protect from infection. Here, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although, binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime- gp120 boost vaccination elicited polyfunctional, non-neutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge.IMPORTANCEThe antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine, and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model.
Saunders, KO, Santra, S, Parks, R, Yates, NL, Sutherland, LL, Scearce, RM, Balachandran, H, Bradley, T, Goodman, D, Eaton, A, Stanfield-Oakley, SA, Tartaglia, J, Phogat, S, Pantaleo, G, Esteban, M, Gomez, CE, Perdiguero, B, Jacobs, B, Kibler, K, Korber, B, Montefiori, DC, Ferrrari, G, Vandergrift, N, Liao, H-X, Tomaras, GD, and Haynes, BF. "Immunogenicity of NYVAC prime-protein boost HIV-1 envelope vaccination and SHIV challenge of nonhuman primates." Journal of virology (February 7, 2018).