Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection |
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Authors: | Lakhashe Samir K Wang Wendy Siddappa Nagadenahalli B Hemashettar Girish Polacino Patricia Hu Shiu-Lok Villinger François Else James G Novembre Francis J Yoon John K Lee Sandra J Montefiori David C Ruprecht Ruth M Rasmussen Robert A |
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Institution: | Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America. |
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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. |
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