Reduced SARS-CoV-2 mRNA vaccine immunogenicity and protection in mice with diet-induced obesity and insulin resistance.

Autor: O'Meara TR; Precision Vaccines Program, Boston Children's Hospital, Boston, Mass., Nanishi E; Precision Vaccines Program, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass., McGrath ME; Department of Microbiology and Immunology, Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, Md., Barman S; Precision Vaccines Program, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass., Dong D; Precision Vaccines Program, Boston Children's Hospital, Boston, Mass., Dillen C; Department of Microbiology and Immunology, Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, Md., Menon M; Precision Vaccines Program, Boston Children's Hospital, Boston, Mass., Seo HS; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Mass., Dhe-Paganon S; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Mass., Ernst RK; Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Md., Levy O; Precision Vaccines Program, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass; Broad Institute of MIT and Harvard, Cambridge, Mass., Frieman MB; Department of Microbiology and Immunology, Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, Md., Dowling DJ; Precision Vaccines Program, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address: david.dowling@childrens.harvard.edu.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2023 Nov; Vol. 152 (5), pp. 1107-1120.e6. Date of Electronic Publication: 2023 Aug 16.
DOI: 10.1016/j.jaci.2023.06.031
Abstrakt: Background: Obesity and type 2 diabetes mellitus (T2DM) are associated with an increased risk of severe outcomes from infectious diseases, including coronavirus disease 2019. These conditions are also associated with distinct responses to immunization, including an impaired response to widely used severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines.
Objective: We sought to establish a connection between reduced immunization efficacy via modeling the effects of metabolic diseases on vaccine immunogenicity that is essential for the development of more effective vaccines for this distinct vulnerable population.
Methods: A murine model of diet-induced obesity and insulin resistance was used to model the effects of comorbid T2DM and obesity on vaccine immunogenicity and protection.
Results: Mice fed a high-fat diet (HFD) developed obesity, hyperinsulinemia, and glucose intolerance. Relative to mice fed a normal diet, HFD mice vaccinated with a SARS-CoV-2 mRNA vaccine exhibited significantly lower anti-spike IgG titers, predominantly in the IgG2c subclass, associated with a lower type 1 response, along with a 3.83-fold decrease in neutralizing titers. Furthermore, enhanced vaccine-induced spike-specific CD8 + T-cell activation and protection from lung infection against SARS-CoV-2 challenge were seen only in mice fed a normal diet but not in HFD mice.
Conclusions: The study demonstrated impaired immunity following SARS-CoV-2 mRNA immunization in a murine model of comorbid T2DM and obesity, supporting the need for further research into the basis for impaired anti-SARS-CoV-2 immunity in T2DM and investigation of novel approaches to enhance vaccine immunogenicity among those with metabolic diseases.
Competing Interests: Disclosure statement This study was supported, in part, by the National Institutes of Health (NIH)/National Institutes of Allergy and Infectious Diseases awards, including Adjuvant Discovery (award nos. HHSN272201400052C and 75N93019C00044) and Development (award no. HHSN272201800047C) Program Contracts, a Massachusetts Consortium on Pathogen Readiness award to O.L.; an NIH grant (grant no. 1R21AI137932-01A1) and Adjuvant Discovery Program contract (75N93019C00044) to D.J.D.; and Biomedical Advanced Research and Development Authority ASPR-20-01495, Defense Advanced Research Projects Agency ASPR-20-01495, NIH R01 AI148166, and NIH HHSN272201400007C to M.B.F. The Precision Vaccines Program is supported, in part, by the Department of Pediatrics of Boston Children’s Hospital and the Chief Scientific Office. Work within the Precision Vaccines Program on this project was funded in part by philanthropic support from Amy and Michael Barry, Stop & Shop, and the Boston Investment Conference. Disclosure of potential conflict of interest: E. Nanishi, T. R. O’Meara, O. Levy, and D. J. Dowling are named inventors on vaccine adjuvant patents assigned to Boston Children’s Hospital, including one titled “Adjuvants for Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV) Vaccines” (PCT/US21/34919). M. B. Frieman is on the scientific advisory board of Aikido Pharma and has collaborative research agreements with Novavax, AstraZeneca, Regeneron, and Irazu Bio. O. Levy (Levy laboratory) has received a sponsored research agreement from GlaxoSmithKline and has served as a paid consultant to Moody’s Analytics. D. J. Dowling is on the scientific advisory board of EdJen BioTech; and serves as a consultant with Merck Research Laboratories/Merck Sharp & Dohme Corp (a subsidiary of Merck & Co, Inc). These commercial or financial relationships are unrelated to the present study. The rest of the authors declare that they have no relevant conflicts of interest.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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