The mRNA vaccine BNT162b2 demonstrates impaired T H 1 immunogenicity in human elders in vitro and aged mice in vivo .
| Autor: | Brook B; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Fatou B; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Kumar Checkervarty A; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Prevention of Organ Failure (PROOF) Centre of Excellence, St Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.; UBC Centre for Heart Lung Innovation, Providence Research, St Paul's Hospital, Vancouver, BC, Canada., Barman S; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Sweitzer C; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA., Bosco AN; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA., Sherman AC; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Baden LR; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Morrocchi E; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Sanchez-Schmitz G; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Palma P; Bambino Gesù Children's Hospital, Rome, Italy.; Chair of Pediatrics, University of Rome, Tor Vergata, Italy., Nanishi E; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., O'Meara TR; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA., McGrath ME; Center for Pathogen Research, Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, USA., Frieman MB; Center for Pathogen Research, Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, USA., Soni D; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., van Haren SD; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Ozonoff A; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Diray-Arce J; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Steen H; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Dowling DJ; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Levy O; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT & Harvard, Cambridge, MA, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Research square [Res Sq] 2022 Dec 21. Date of Electronic Publication: 2022 Dec 21. |
| DOI: | 10.21203/rs.3.rs-2395118/v1 |
| Abstrakt: | mRNA vaccines have been key to addressing the SARS-CoV-2 pandemic but have impaired immunogenicity and durability in vulnerable older populations. We evaluated the mRNA vaccine BNT162b2 in human in vitro whole blood assays with supernatants from adult (18-50 years) and elder (≥60 years) participants measured by mass spectrometry and proximity extension assay proteomics. BNT162b2 induced increased expression of soluble proteins in adult blood (e.g., C1S, PSMC6, CPN1), but demonstrated reduced proteins in elder blood (e.g., TPM4, APOF, APOC2, CPN1, and PI16), including 30-85% lower induction of T Competing Interests: Competing interests O.L. has served as a paid consultant to Moody’s Analytics and the Midsized Bankers Association of America. 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., S.H., O.L., and D.J.D. are named inventors on vaccine adjuvant patent(s). O.L. and G.S.S. are recipients of a sponsored research agreement with GlaxoSmithKline (GSK) and inventors on a patent for a human in vitro tissue construct system that models vaccine action. 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.). 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. |
| Databáze: | MEDLINE |
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