Genomic diversity contributes to the neuroinvasiveness of the Yellow fever French neurotropic vaccine

Autor: Bakoa, Florian, Préhaud, Christophe, Beauclair, Guillaume, Chazal, Maxime, Mantel, Nathalie, Lafon, Monique, Jouvenet, Nolwenn
Přispěvatelé: Neuro-Immunologie Virale - Viral Neuro-immunology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Sanofi Pasteur [Marcy-l'Étoile, France], Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Signalisation antivirale - Virus sensing and signaling, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), We thank the Association Nationale de la Recherche et de la Technologie (CIFRE 2017/0314), Sanofi-Pasteur and Institut Pasteur for funding., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: NPJ vaccines
NPJ vaccines, Nature Research 2021, 6 (1), pp.64. ⟨10.1038/s41541-021-00318-3⟩
NPJ vaccines, 2021, 6 (1), pp.64. ⟨10.1038/s41541-021-00318-3⟩
npj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021)
NPJ Vaccines
ISSN: 2059-0105
Popis: International audience; Mass vaccination with the live attenuated vaccine YF-17D is the current way to prevent infection with Yellow fever virus (YFV). However, 0.000012-0.00002% of vaccinated patients develop post-vaccination neurological syndrome (YEL-AND). Understanding the factors responsible for neuroinvasion, neurotropism, and neurovirulence of the vaccine is critical for improving its biosafety. The YF-FNV vaccine strain, known to be associated with a higher frequency of YEL-AND (0.3-0.4%) than YF-17D, is an excellent model to study vaccine neuroinvasiveness. We determined that neuroinvasiveness of YF-FNV occured both via infection and passage through human brain endothelial cells. Plaque purification and next generation sequencing (NGS) identified several neuroinvasive variants. Their neuroinvasiveness was not higher than that of YF-FNV. However, rebuilding the YF-FNV population diversity from a set of isolated YF-FNV-N variants restored the original neuroinvasive phenotype of YF-FNV. Therefore, we conclude that viral population diversity is a critical factor for YFV vaccine neuroinvasiveness.
Databáze: OpenAIRE
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