The Ebola virus disease is one of the most dangerous diseases to develop into a major health concern in the modern era, largely because of the ZEBOV outbreak that has devastated West Africa from 2014 to 2016. The outbreak has compelled many countries and organizations to prioritize finding a vaccine for Ebola, which is key to preventing a similar outbreak on a global scale. As a result, studies on Ebola vaccines have increased in frequency since 2014. This thesis will focus on three vaccine candidates that could potentially be developed into a future vaccine for Ebola: chAd3, rVSV, and rAd5. Each of the vaccines has been the focus of several studies on both animals and humans, which have provided information and understanding of the vaccines’ characteristics in terms of reactogenicity and immunogenicity. All of the vaccines demonstrate safety and immunogenicity profiles that offer promise for the vaccines as future candidates, which at first makes them seem very similar to each other. However, they each differ substantially in their flaws and ability to generate an immunogenic response. More specifically, the chAd3 vaccine requires a boost of MVA to reach its full potential, the rVSV vaccine has expressed a higher level of reactogenicity and adverse effects than the other two vaccines, and the rAd5 vaccine’s efficacy is weakened by the presence of pre-existing immunity against Ad5 in the human population.

Ebolavirus (EBOV) est un filovirus responsable de fièvres hémorragiques virales sévères chez l’humain, qui peuvent être létales dans 90% des cas. L’actuelle épidémie en République Démocratique du Congo et l’ampleur démesurée de l'épidémie de 2014-2016 en Afrique de l’Ouest, qui a causé la mort de plus de 11 000 personnes, ont poussé les agences sanitaires internationales à tester plusieurs approches thérapeutiques afin d’essayer d’endiguer rapidement la propagation virale et de limiter la mortalité liée au virus lors de futures épidémies. Parmi toutes les stratégies testées, le virus recombinant réplicatif rVSV-ZEBOV qui exprime la glycoprotéine de surface d’EBOV, semble offrir la meilleur protection, aussi bien en modèle animaliers que sur le terrain. Avant d’être testé chez l’humain, de nombreuses études ont permis de mettre en évidence l’efficacité et l’innocuité de ce vaccin prototype. Pourtant et malgré le fait que de nombreuses études ont démontré l’importance et le rôle de la glycoprotéine GP dans l’efficacité des vaccins contre ce virus, aucune étude n’a encore été réalisé sur la nature des glycoprotéines virales synthétisées par le gène GP d’EBOV inséré dans le génome du virus VSV. Ainsi, les caractérisations moléculaires des protéines virales produites lors de l’infection par le virus rVSV-GP décrites dans ces travaux de thèse offrent de nouvelles perspectives pour comprendre le succès de ce vaccin mais aussi l’origine virales dans les effets secondaires sévères observés lors de la vaccination, et pourront aider à développer un vaccin plus sûr, qui n’est actuellement pas utilisable chez les personnes immunodéprimées / The filovirus Ebolavirus (EBOV) is the causative agent of severe viral hemorrhagic fevers in humans that can be lethal in 90% of cases. The current outbreak in the Democratic Republic of Congo and the extraordinary scale of the 2014-2016 outbreak in West Africa, that caused the death of more than 11 000 disease victims, lead the international public health agencies to test several therapeutic approach to limit viral spreading and mortality. Amongst those, the recombinant replication-competent rVSV-ZEBOV virus, that expressed EBOV GP glycoprotein, appears to offer the best protection in animal models and outbreak settings. While its effectiveness and safety have been widely investigated before human trials and despite numerous studies that showed the importance the nature of the glycoproteins which are produced during the infection from the EBOV GP gene that has been inserted in VSV genome are unknown. In this respect, the molecular characterisations of the viral glycoproteins synthesised during rVSV-GP presented in this thesis, offer new insights with which to understand the success of the rVSV-GP vaccine but also the potential viral origins of the severe adverse side effects observed during vaccination and could help in developing a safer vaccine, which currently cannot be used in an immunocompromised population

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