Vaccination against Heterologous R5 Clade C SHIV: Prevention of Infection and Correlates of Protection | Zendy

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

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Vaccination against Heterologous R5 Clade C SHIV: Prevention of Infection and Correlates of Protection

Author(s) -

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

Publication year - 2011

Publication title -

plos one

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.99

H-Index - 332

ISSN - 1932-6203

DOI - 10.1371/journal.pone.0022010

Subject(s) - viremia , virology , immunogen , simian immunodeficiency virus , vaccination , biology , immunology , heterologous , immune system , neutralizing antibody , aids vaccines , virus , vaccine efficacy , antibody , vaccine trial , monoclonal antibody , biochemistry , gene

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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