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A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine
Journal article   Open access   Peer reviewed

A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine

Adam-Nicolas Pelletier, Gabriela Pacheco Sanchez, Abdullah Izmirly, Mark Watson, Tiziana Di Pucchio, Karina Inacio Carvalho, Abdelali Filali-Mouhim, Eustache Paramithiotis, Maria do Carmo S. T. Timenetsky, Alexander Roberto Precioso, …
Cell reports (Cambridge), v 43(7), 114370
23 Jul 2024
PMID: 38900640
url
https://doi.org/10.1016/j.celrep.2024.114370View
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Science & Technology Cell Biology
Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identifies a multi-OMICs pre-vaccination signature and mechanisms predictive of broad antibody responses after immunization with a tetravalent live attenuated DENV vaccine candidate (Butantan-DV/ TV003). Anti-inflammatory pathways, including TGF-b signaling expressed by CD68low low monocytes, and the metabolites phosphatidylcholine (PC) and phosphatidylethanolamine (PE) positively correlate with broadly neutralizing antibody responses against DENV. In contrast, expression of pro-inflammatory pathways and cytokines (IFN and IL-1) in CD68hi hi monocytes and primary and secondary bile acids negatively correlates with broad DENV-specific antibody responses. Induction of TGF-b and IFNs is done respectively by PC/ PE and bile acids in CD68low low and CD68hi hi monocytes. The inhibition of viral sensing by PC/PE-induced TGF-b is confirmed in vitro. . Our studies show that the balance between metabolites and the pro- or anti-inflammatory state of innate immune cells drives broad and protective B cell response to a live attenuated dengue vaccine.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
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