Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant

Susan W. Barnett, Brian Burke, Yide Sun, Elaine Kan, Harold Legg, Ying Lian, Kristen Bost, Fengmin Zhou, Amanda Goodsell, Jan Zur Megede, John Polo, John Donnelly, Jeffrey Ulmer, Gillis R. Otten, Chris J Miller, Michael Vajdy, Indresh K. Srivastava

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIVSF162P4 following sequential immunization with alphavirus replicon particles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1SF162 gp140ΔV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIVSF162P4 (intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against HIV infection at a relevant mucosal portal of entry.

Original languageEnglish (US)
Pages (from-to)5975-5985
Number of pages11
JournalJournal of Virology
Volume84
Issue number12
DOIs
StatePublished - Jun 2010

ASJC Scopus subject areas

  • Immunology
  • Virology

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    Barnett, S. W., Burke, B., Sun, Y., Kan, E., Legg, H., Lian, Y., Bost, K., Zhou, F., Goodsell, A., Zur Megede, J., Polo, J., Donnelly, J., Ulmer, J., Otten, G. R., Miller, C. J., Vajdy, M., & Srivastava, I. K. (2010). Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant. Journal of Virology, 84(12), 5975-5985. https://doi.org/10.1128/JVI.02533-09