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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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

mRNA 疫苗在易受影响的老年人群中显示出免疫原性和持久性受损。我们假设人体体外建模和蛋白质组学可以阐明特定年龄的 mRNA 疫苗作用。BNT162b2 刺激改变了年轻人（18-50 岁）和老年人（≥60 岁）血液样本的血浆蛋白质组，并通过质谱分析、近距离延伸测定和多重分析进行了评估。年轻人的上调（如 PSMC6、CPN1）与老年人的诱导减少（如 TPM4、APOF、APOC2、CPN1、PI16）形成鲜明对比。老年人血液中诱导的 TH1 极化细胞因子和趋化因子（如 IFNγ、CXCL10）降低了 30-85%。老年人样本中含量较低的分析物包括人体内 mRNA 免疫原性生物标记物（如 IFNγ、CXCL10、CCL4、IL-1RA）。BNT162b2 还显示，老年小鼠与年轻成年小鼠的 CD4+ TH1 反应减少。我们的研究证明了人类体外平台模拟年龄特异性 mRNA 疫苗免疫原性的实用性，强调了老年人对 TH1 极化的支持受损，并为精确 mRNA 疫苗佐剂诱导更大的免疫原性提供了理论依据。

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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