The BNT162b2 mRNA vaccine demonstrates reduced age-associated T H 1 support in vitro and in vivo .

Autor: Brook B; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA., Checkervarty AK; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Prevention of Organ Failure (PROOF) Centre of Excellence, St Paul's Hospital, University of British Columbia, Vancouver, BC V6Z 2K5, Canada.; UBC Centre for Heart Lung Innovation, Providence Research, St Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada., Barman S; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA., Sweitzer C; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA., Bosco AN; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA., Sherman AC; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA., Baden LR; Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA., Morrocchi E; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Sanchez-Schmitz G; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA., Palma P; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.; Department of Systems Medicine- Chair of Pediatrics, University of Rome, 00133 Tor Vergata, Italy., Nanishi E; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA., O'Meara TR; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA., McGrath ME; Center for Pathogen Research, Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA., Frieman MB; Center for Pathogen Research, Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA., Soni D; Global Investigative Toxicology, Preclinical Safety, Sanofi, Cambridge, MA 02142, USA., van Haren SD; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA., Ozonoff A; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.; Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA., Diray-Arce J; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA., Steen H; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Dowling DJ; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA., Levy O; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.; Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA.
Jazyk: angličtina
Zdroj: IScience [iScience] 2024 Sep 26; Vol. 27 (11), pp. 111055. Date of Electronic Publication: 2024 Sep 26 (Print Publication: 2024).
DOI: 10.1016/j.isci.2024.111055
Abstrakt: mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human in vitro modeling and proteomics could elucidate age-specific mRNA vaccine actions. BNT162b2-stimulation changed the plasma proteome of blood samples from young (18-50Y) and older adult (≥60Y) participants, assessed by mass spectrometry, proximity extension assay, and multiplex. Young adult up-regulation (e.g., PSMC6, CPN1) contrasted reduced induction in older adults (e.g., TPM4, APOF, APOC2, CPN1, PI16). 30-85% lower T H 1-polarizing cytokines and chemokines were induced in elderly blood (e.g., IFNγ, CXCL10). Analytes lower in older adult samples included human in vivo mRNA immunogenicity biomarkers (e.g., IFNγ, CXCL10, CCL4, IL-1RA). BNT162b2 also demonstrated reduced CD4 + T H 1 responses in aged vs. young adult mice. Our study demonstrates the utility of human in vitro platforms modeling age-specific mRNA vaccine immunogenicity, highlights impaired support of T H 1 polarization in older adults, and provides a rationale for precision mRNA vaccine adjuvantation to induce greater immunogenicity.
Competing Interests: O.L. has served as a consultant to GlaxoSmithKline (GSK) and Hillevax. M.B.F. serves on the scientific advisory board of Aikido Pharma and has collaborative research agreements with Novavax, AstraZeneca, Regeneron, and Irazu Bio. B.B., E.N., T.R.O., D.S., S.H., O.L., and D.J.D. are named inventors on vaccine adjuvant patent(s). O.L., G.S.S., and D.J.D. are named inventors on patents related to human in vitro modeling of vaccine responses. O.L. and G.S.S. are recipients of a sponsored research agreement with GSK. D.J.D 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.). O.L. and D.J.D. are co-founders of and advisors to Ovax, Inc. ACS and LRB are involved in HIV, COVID, and other vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), COVID Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, and Sanofi. These commercial or financial relationships are unrelated to the current study. The participating Precision Vaccines Program (PVP) laboratories were supported in part, by U.S. National Institutes of Health (NIH)/National Institutes of Allergy and Infectious Diseases (NIAID) awards, including Human Immunology Project Consortium award U19 AI118608, Adjuvant Discovery (HHSN272201400052C) and Development (HHSN272201800047C) Program Contracts to O.L.; Adjuvant Discovery Program contract (75N93019C00044) to O.L. and D.J.D as well as NIH grant (1R21AI137932-01A1) to D.J.D. O.L. is also funded by an award from the Coalition for Epidemic Preparedness Innovations (CEPI), via the International Network of Special Immunization Services (INSIS). The PVP is supported, in part, by the BCH Department of Pediatrics and philanthropy via the BCH Trust, including from the Barry Family and the Boston Investment Council. A.K.C. was supported by the Friedman Award for Scholars in Health, the University of British Columbia, and Mitacs Accelerate Canada.
(© 2024 The Author(s).)
Databáze: MEDLINE
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