The BNT162b2 mRNA vaccine demonstrates reduced age-associated TH1 support in vitro and in vivo
iScience, 2024
Brook B., Checkervarty A., Barman S., Sweitzer C., Bosco A., Sherman A., Baden L., Morrocchi E., Sanchez-Schmitz G., Palma P., Nanishi E., O’Meara T., McGrath M., Frieman M., Soni D., van Haren S., Ozonoff A., Diray-Arce J., Steen H., Dowling D., Levy O.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Cell Culture Supernatant |  Olink Target 96 |
Abstract
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 TH1-polarizing cytokines and chemokines were induced in elder 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+ TH1 responses in aged vs young adult mice. Our study demonstrates the utility of human in vitro platforms modelling age-specific mRNA vaccine immunogenicity, highlights impaired support of TH1 polarization in older adults, and provides rationale for precision mRNA vaccine adjuvantation to induce greater immunogenicity.