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

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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536681/
https://www.ncbi.nlm.nih.gov/pubmed/34686669
http://dx.doi.org/10.1038/s41541-021-00385-6
Descripción
Sumario: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.