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Article Abstract
mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human 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 T1-polarizing cytokines and chemokines were induced in elderly blood (e.g., IFNγ, CXCL10). Analytes lower in older adult samples included human mRNA immunogenicity biomarkers (e.g., IFNγ, CXCL10, CCL4, IL-1RA). BNT162b2 also demonstrated reduced CD4 T1 responses in aged vs. young adult mice. Our study demonstrates the utility of human platforms modeling age-specific mRNA vaccine immunogenicity, highlights impaired support of T1 polarization in older adults, and provides a rationale for precision mRNA vaccine adjuvantation to induce greater immunogenicity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576392 | PMC |
| http://dx.doi.org/10.1016/j.isci.2024.111055 | DOI Listing |
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