A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine.
| Autor: | 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. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Cell reports [Cell Rep] 2024 Jul 23; Vol. 43 (7), pp. 114370. Date of Electronic Publication: 2024 Jun 18. |
| DOI: | 10.1016/j.celrep.2024.114370 |
| Abstrakt: | 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 CD68 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 CD68 hi 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 CD68 low and CD68 hi 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. Competing Interests: Declaration of interests A.-N.P. is a paid bioinformatics consultant and owner of RPM Bioinfo Solutions. M.S.D. is a consultant or advisor for Inbios, Vir Biotechnology, Ocugen, IntegerBio, GlaxoSmithKline, Allen & Overy LLP, Moderna, and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Emergent BioSolutions, IntegerBio, and Moderna. E.G.K. is the current director of the Butantan Institute, which is the vaccine manufacturer. E.P. is a shareholder of CellCarta Biosciences, Inc. T.D.P. is currently employed by MacroGenics, Inc. (Rockville, MD), and received stock options as a condition of employment. R.P.S. is a member of the scientific advisory board for CellCarta. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|