TY - JOUR
T1 - A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine
AU - Pelletier, Adam Nicolas
AU - Sanchez, Gabriela Pacheco
AU - Izmirly, Abdullah
AU - Watson, Mark
AU - Di Pucchio, Tiziana
AU - Carvalho, Karina Inacio
AU - Filali-Mouhim, Abdelali
AU - Paramithiotis, Eustache
AU - Timenetsky, Maria do Carmo S.T.
AU - Precioso, Alexander Roberto
AU - Kalil, Jorge
AU - Diamond, Michael S.
AU - Haddad, Elias K.
AU - Kallas, Esper G.
AU - Sekaly, Rafick Pierre
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/7/23
Y1 - 2024/7/23
N2 - 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.
AB - 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.
KW - CP: Immunology
KW - bile acids
KW - dengue
KW - immunology
KW - systems biology
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85196203824&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2024.114370
DO - 10.1016/j.celrep.2024.114370
M3 - Article
C2 - 38900640
AN - SCOPUS:85196203824
SN - 2639-1856
VL - 43
JO - Cell Reports
JF - Cell Reports
IS - 7
M1 - 114370
ER -