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Caractérisation des génomes défectifs de la plateforme vaccinale rougeole et intérêt pour le développement d'un vaccin antipaludique

Abstract : Measles virus has been attenuated in the 60s after multiple passages in chicken embryocell culture. It is one of the most efficient and safe vaccines, conferring life-long protection. Thanks to reverse genetics revolution, it is now used as an efficient viral vaccine platform that open new opportunities to develop vaccines against emerging orneglected diseases, as malaria, which remains an issue for global health but also for the French armed forces. The molecular bases of measles attenuation are still not fully elucidated, but mainly lie on type-I interferon (IFN-I) stimulation and cellular tropism.IFN-I stimulation by vaccine strains was linked to the presence of defective interfering genomes (DI-RNAs). Thus, we characterized the DI-RNAs produced by various recombinant measles viruses and studied their immunostimulatory properties after their specific recognition by immune sensors of innate immunity RIG-I and LGP2. Modification of cellular tropism has long been described as dependent on human ubiquitous CD46 receptor. Nevertheless, we showed in vivo on murine model thathCD46 is not required for measles vaccine replication and that only IFN-I restricted host susceptibility. Finally, we developed an antimalarial vaccine strategy using measles vector by using adjuvant effect of DI-RNAs naturally produced by recombinant measlesvaccines.
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  • HAL Id : tel-02868691, version 1

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Marie Mura. Caractérisation des génomes défectifs de la plateforme vaccinale rougeole et intérêt pour le développement d'un vaccin antipaludique. Virologie. Université Sorbonne Paris Cité, 2018. Français. ⟨NNT : 2018USPCC255⟩. ⟨tel-02868691v1⟩

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