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A recombinant measles virus vaccine strongly reduces SHIV viremia and virus reservoir establishment in macaques

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Nzounza, Patrycja | Martin, Grégoire | Dereuddre-Bosquet, Nathalie | Najburg, Valérie | Gosse, Leslie | Ruffié, Claude | Combredet, Chantal | Petitdemange, Caroline | Souquère, Sylvie | Schlecht-Louf, Géraldine | Moog, Christiane | Pierron, Gérard | Le Grand, Roger | Heidmann, Thierry | Tangy, Frédéric

Edité par CCSD ; Nature Research -

International audience. Replicative vectors derived from live-attenuated measles virus (MV) carrying additional non-measles vaccine antigens have long demonstrated safety and immunogenicity in humans despite pre-existing immunity to measles. Here, we report the vaccination of cynomolgus macaques with MV replicative vectors expressing simian-human immunodeficiency virus Gag, Env, and Nef antigens (MV-SHIV Wt) either wild type or mutated in the immunosuppressive (IS) domains of Nef and Env antigens (MV-SHIV Mt). We found that the inactivation of Nef and Env IS domains by targeted mutations led to the induction of significantly enhanced post-prime cellular immune responses. After repeated challenges with low doses of SHIV-SF162p3, vaccinees were protected against high viremia, resulting in a 2-Log reduction in peak viremia, accelerated viral clearance, and a decrease -even complete protection for nearly half of the monkeys- in reservoir cell infection. This study demonstrates the potential of a replicative viral vector derived from the safe and widely used measles vaccine in the development of a future human vaccine against HIV-1.

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