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.
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页数：23
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