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, Jorge Kalil, Michael S. Diamond, Elias K. Haddad, Esper G. Kallas, Rafick Pierre Sekaly

Research output: Contribution to journalArticlepeer-review

Abstract

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-β signaling expressed by CD68low 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 monocytes and primary and secondary bile acids negatively correlates with broad DENV-specific antibody responses. Induction of TGF-β and IFNs is done respectively by PC/PE and bile acids in CD68low and CD68hi monocytes. The inhibition of viral sensing by PC/PE-induced TGF-β 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.

Original languageEnglish
Article number114370
JournalCell Reports
Volume43
Issue number7
DOIs
StatePublished - Jul 23 2024

Keywords

  • CP: Immunology
  • bile acids
  • dengue
  • immunology
  • systems biology
  • vaccine

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