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

被引：0

作者：

Pelletier, Adam-Nicolas ^{[1
,2
]}

Sanchez, Gabriela Pacheco ^{[3
]}

Izmirly, Abdullah ^{[4
,7
]}

Watson, Mark ^{[5
]}

Di Pucchio, Tiziana ^{[3
]}

Carvalho, Karina Inacio ^{[2
,6
]}

Filali-Mouhim, Abdelali

Paramithiotis, Eustache ^{[5
]}

Timenetsky, Maria do Carmo S. T. ^{[8
]}

Precioso, Alexander Roberto ^{[9
]}

Kalil, Jorge ^{[10
,11
]}

Diamond, Michael S. ^{[12
,13
,14
]}

Haddad, Elias K. ^{[15
]}

Kallas, Esper G. ^{[9
,16
]}

Sekaly, Rafick Pierre ^{[3
]}

机构：

[1] RPM Bioinfo Solut, St Therese, PQ, Canada

[2] Case Western Reserve Univ, Dept Pathol, Sch Med, Cleveland, OH USA

[3] Emory Univ, Sch Med, Dept Pathol & Lab Med, Pathol Adv Translat Res Unit, Atlanta, GA 30322 USA

[4] King Abdulaziz Univ, Fac Appl Med Sci, Dept Med Lab Sci, Jeddah, Saudi Arabia

[5] CellCarta, Montreal, PQ, Canada

[6] Hosp Israelita Albert Einstein, Sao Paulo, SP, Brazil

[7] Ctr Rech Ctr hosp Univ Montreal CRCHUM, Montreal, PQ, Canada

[8] Adolfo Lutz Inst, Sao Paulo, Brazil

[9] Inst Butantan, Sao Paulo, Brazil

[10] Hosp Clin Fac Med Univ Sao Paulo HCFMUSP, Lab Immunol Heart Inst InCor, Sao Paulo, SP, Brazil

[11] Inst Nacl Ciencia & Tecnol III INCT, Inst Invest Immunol, Sao Paulo, SP, Brazil

[12] Washington Univ, Dept Med, Sch Med, St Louis, MO USA

[13] Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO USA

[14] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO USA

[15] Drexel Univ, Dept Med & Microbiol & Immunol, Coll Med, Philadelphia, PA USA

[16] Univ Sao Paulo, Dept Infect & Parasit Dis, Med Sch, Clin Hosp, BR-01246903 Sao Paulo, Brazil

来源：

CELL REPORTS | 2024年 / 43卷 / 07期

关键词：

YELLOW-FEVER VACCINE; SYSTEMS BIOLOGY; DEPENDENT ENHANCEMENT; GUT MICROBIOME; TGF-BETA; RIG-I; INFECTION; RECEPTOR; ACTIVATION; PHOSPHATIDYLCHOLINE;

D O I：

10.1016/j.celrep.2024.114370

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：23

共 33 条

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