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

Cell Reports (Jul 2024)

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

Affiliations

Adam-Nicolas Pelletier: RPM Bioinfo Solutions, Sainte-Thérèse, QC, Canada; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Gabriela Pacheco Sanchez: Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Abdullah Izmirly: Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Mark Watson: CellCarta, Montreal, QC, Canada
Tiziana Di Pucchio: Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Karina Inacio Carvalho: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
Abdelali Filali-Mouhim: Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada
Eustache Paramithiotis: CellCarta, Montreal, QC, Canada
Maria do Carmo S.T. Timenetsky: Instituto Adolfo Lutz, São Paulo, Brazil
Alexander Roberto Precioso: Instituto Butantan, São Paulo, Brazil
Jorge Kalil: Laboratory of Immunology, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil; Institute for Investigation in Immunology-Instituto Nacional de Ciência e Tecnologia-iii-INCT, São Paulo, SP, Brazil
Michael S. Diamond: Departments of Medicine, Molecular Microbiology, and Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Elias K. Haddad: Department of Medicine and Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA
Esper G. Kallas: Instituto Butantan, São Paulo, Brazil; Department of Infectious and Parasitic Diseases, Hospital das Clínicas, School of Medicine, University of Sao Paulo, São Paulo 01246-903, Brazil
Rafick Pierre Sekaly: Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 7
p. 114370

Abstract

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Summary: 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.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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