The BNT162b2 mRNA vaccine demonstrates reduced age-associated TH1 support in vitro and in vivo

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-11-15 DOI:10.1016/j.isci.2024.111055

Byron Brook , Abhinav Kumar Checkervarty , Soumik Barman , Cali Sweitzer , Anna-Nicole Bosco , Amy C. Sherman , Lindsey R. Baden , Elena Morrocchi , Guzman Sanchez-Schmitz , Paolo Palma , Etsuro Nanishi , Timothy R. O’Meara , Marisa E. McGrath , Matthew B. Frieman , Dheeraj Soni , Simon D. van Haren , Al Ozonoff , Joann Diray-Arce , Hanno Steen , David J. Dowling , Ofer Levy

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引用次数: 0

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 T_H1-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_H1 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_H1 polarization in older adults, and provides a rationale for precision mRNA vaccine adjuvantation to induce greater immunogenicity.

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BNT162b2 mRNA 疫苗在体外和体内都能降低年龄相关的 TH1 支持率

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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