A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine.
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-beta 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-beta 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-beta 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.
| Authors: | Pelletier AN, Sanchez GP, Izmirly A, Watson M, Di Pucchio T, Carvalho KI, Filali-Mouhim A, Paramithiotis E, Timenetsky MDCST, Precioso AR, Kalil J, Diamond MS, Haddad EK, Kallas EG, Sekaly RP, |
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| Journal: | Cell Rep;2024Jul23; 43 (7) 114370. doi:10.1016/j.celrep.2024.114370 |
| Year: | 2024 |
| PubMed: | PMID: 38900640 (Go to PubMed) |