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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lakhashe, SK; Wang, W; Siddappa, NB; Hemashettar, G; Polacino, P; Hu, S-L; Villinger, F; Else, JG; Novembre, FJ; Yoon, JK; Lee, SJ; Montefiori, DC; Ruprecht, RM; Rasmussen, RA

Published Date

  • 2011

Published In

Volume / Issue

  • 6 / 7

Start / End Page

  • e22010 -

PubMed ID

  • 21799765

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0022010

Language

  • eng

Conference Location

  • United States