The BNT162b2 mRNA vaccine demonstrates reduced age-associated TH1 support in vitro and in vivo
mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human <i>in vitro</i> 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<sub>H</sub>1-polarizing cytokines and chemokines were induced in elderly blood (e.g., IFNγ, CXCL10). Analytes lower in older adult samples included human <i>in vivo</i> mRNA immunogenicity biomarkers (e.g., IFNγ, CXCL10, CCL4, IL-1RA). BNT162b2 also demonstrated reduced CD4<sup>+</sup> T<sub>H</sub>1 responses in aged vs. young adult mice. Our study demonstrates the utility of human <i>in vitro</i> platforms modeling age-specific mRNA vaccine immunogenicity, highlights impaired support of T<sub>H</sub>1 polarization in older adults, and provides a rationale for precision mRNA vaccine adjuvantation to induce greater immunogenicity.
Authors
- Joann Diray‐Arce (ORCID: https://orcid.org/0000-0003-2183-4269)
- Hanno Steen (ORCID: https://orcid.org/0000-0003-0179-6648)
- Simon D. van Haren (ORCID: https://orcid.org/0000-0002-1791-0161)
- Elena Morrocchi (ORCID: https://orcid.org/0000-0002-3243-9291)
- David J. Dowling (ORCID: https://orcid.org/0000-0003-1095-6156)
- Paolo Palma (ORCID: https://orcid.org/0000-0002-3066-4719)
- Soumik Barman (ORCID: https://orcid.org/0000-0002-3641-2125)
- Timothy R. O’Meara (ORCID: https://orcid.org/0000-0002-3651-5167)
- Matthew B. Frieman (ORCID: https://orcid.org/0000-0003-0107-0775)
- Cali Sweitzer (ORCID: https://orcid.org/0000-0002-7941-215X)
- Guzman Sánchez‐Schmitz (ORCID: https://orcid.org/0000-0002-3566-7505)
- Anna-Nicole Bosco
- Amy C Sherman (ORCID: https://orcid.org/0000-0002-6075-3990)
- Byron Brook (ORCID: https://orcid.org/0000-0003-3184-8285)
- Ofer Levy (ORCID: https://orcid.org/0000-0002-5859-1945)
- Marisa E. McGrath (ORCID: https://orcid.org/0000-0002-7451-4958)
- Abhinav Kumar Checkervarty (ORCID: https://orcid.org/0000-0002-1032-9198)
- Al Ozonoff (ORCID: https://orcid.org/0000-0003-4233-5899)
- Etsuro Nanishi (ORCID: https://orcid.org/0000-0002-9957-7162)
- Dheeraj Soni (ORCID: https://orcid.org/0000-0002-5555-2051)
- Lindsey Robert Baden (ORCID: https://orcid.org/0009-0004-1752-1926)
Institutions
- Broad Institute (US)
- University of Rome Tor Vergata (IT)
- University of Maryland, Baltimore (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- St. Paul's Hospital (CA)
- Sanofi (France) (FR)
- Bambino Gesù Children's Hospital (IT)
- Prevention of Organ Failure (CA)
Publication Details
- Journal
- iScience
- Published
- 2024-09-26
- DOI
- https://doi.org/10.1016/j.isci.2024.111055
- Citations
- 5
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 2.75
Funders
- National Institutes of Health
- Centers for Disease Control and Prevention
- Japan Society for the Promotion of Science