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A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine.
Pelletier, Adam-Nicolas; Sanchez, Gabriela Pacheco; Izmirly, Abdullah; Watson, Mark; Di Pucchio, Tiziana; Carvalho, Karina Inacio; Filali-Mouhim, Abdelali; Paramithiotis, Eustache; Timenetsky, Maria do Carmo S T; Precioso, Alexander Roberto; Kalil, Jorge; Diamond, Michael S; Haddad, Elias K; Kallas, Esper G; Sekaly, Rafick Pierre.
Afiliação
  • Pelletier AN; RPM Bioinfo Solutions, Sainte-Thérèse, QC, Canada; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Sanchez GP; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
  • Izmirly A; Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Watson M; CellCarta, Montreal, QC, Canada.
  • Di Pucchio T; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
  • Carvalho KI; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
  • Filali-Mouhim A; Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
  • Paramithiotis E; CellCarta, Montreal, QC, Canada.
  • Timenetsky MDCST; Instituto Adolfo Lutz, São Paulo, Brazil.
  • Precioso AR; Instituto Butantan, São Paulo, Brazil.
  • Kalil J; 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.
  • Diamond MS; Departments of Medicine, Molecular Microbiology, and Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Haddad EK; Department of Medicine and Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
  • Kallas EG; 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.
  • Sekaly RP; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: rafick.sekaly@emory.edu.
Cell Rep ; 43(7): 114370, 2024 Jul 23.
Article em En | MEDLINE | ID: mdl-38900640
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-ß 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-ß 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-ß 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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vírus da Dengue / Vacinas contra Dengue / Anticorpos Antivirais Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vírus da Dengue / Vacinas contra Dengue / Anticorpos Antivirais Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos