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- Title
Vaccination against Heterologous R5 Clade C SHIV: Prevention of Infection and Correlates of Protection.
- Authors
Lakhashe, Samir K.; Wendy Wang; Siddappa, Nagadenahalli B.; Hemashettar, Girish; Polacino, Patricia; Shiu-Lok Hu; Villinger, François; Else, James G.; Novembre, Francis J.; Yoon, John K.; Lee, Sandra J.; Montefiori, David C.; Ruprecht, Ruth M.; Rasmussen, Robert A.
- 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.
- Subjects
VACCINATION; HIV; IMMUNE response; AIDS prevention; GAG proteins; VIROLOGY; VIREMIA; HIV antibodies
- Publication
PLoS ONE, 2011, Vol 6, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0022010