Vaccination against heterologous R5 clade C SHIV: Prevention of infection and correlates of protection

Samir K. Lakhashe, Wendy Wang, Nagadenahalli B. Siddappa, Girish Hemashettar, Patricia Polacino, Shiu Lok Hu, François Villinger, James G. Else, Francis J. Novembre, John K. Yoon, Sandra J. Lee, David C. Montefiori, Ruth M. Ruprecht, Robert A. Rasmussen

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.

Original languageEnglish (US)
Article numbere22010
JournalPloS one
Volume6
Issue number7
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Lakhashe, S. K., Wang, W., Siddappa, N. B., Hemashettar, G., Polacino, P., Hu, S. L., Villinger, F., Else, J. G., Novembre, F. J., Yoon, J. K., Lee, S. J., Montefiori, D. C., Ruprecht, R. M., & Rasmussen, R. A. (2011). Vaccination against heterologous R5 clade C SHIV: Prevention of infection and correlates of protection. PloS one, 6(7), [e22010]. https://doi.org/10.1371/journal.pone.0022010