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- Title
A recombinant measles virus vaccine strongly reduces SHIV viremia and virus reservoir establishment in macaques.
- Authors
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
- Abstract
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.
- Subjects
MEASLES vaccines; VIRAL vaccines; RECOMBINANT viruses; MEASLES virus; GENETIC vectors; MACAQUES; VIREMIA
- Publication
NPJ Vaccines, 2021, Vol 6, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-021-00385-6