Differential heterologous immunological effects induced by ChAdOx1-S and BNT162b2 COVID-19 vaccines

IF 3.3 4区医学 Q2 CELL BIOLOGY

Cellular immunology Pub Date : 2025-12-01 Epub Date: 2025-10-27 DOI:10.1016/j.cellimm.2025.105038

Elisabeth A. Dulfer , Büsra Geckin , Martijn Zoodsma , Leonie S. Helder , Wenchao Li , Reinout van Crevel , Josephine S. van der Maat , Yang Li , Jorge Domínguez-Andrés , Mihai G. Netea

{"title":"Differential heterologous immunological effects induced by ChAdOx1-S and BNT162b2 COVID-19 vaccines","authors":"Elisabeth A. Dulfer , Büsra Geckin , Martijn Zoodsma , Leonie S. Helder , Wenchao Li , Reinout van Crevel , Josephine S. van der Maat , Yang Li , Jorge Domínguez-Andrés , Mihai G. Netea","doi":"10.1016/j.cellimm.2025.105038","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The mRNA- and adenovirus-based COVID-19 vaccines may induce different heterologous effects on non-COVID morbidity. We aimed to investigate immunological mechanisms that may account for these differences.</div></div><div><h3>Methods</h3><div>We selected a subgroup of individuals from the TACTIC trial who had completed their COVID-19 vaccination scheme before the introduction of a BNT162b2 booster vaccine. Transcriptional activity, distribution of cell types and cytokine secretion were compared between those who were originally vaccinated with the adenovirus vaccine ChAdOx1-S, and those who had received the mRNA vaccine BNT162b2. Additionally, we investigated how these differences evolved after administration of a BNT162b2 booster vaccine.</div></div><div><h3>Results</h3><div>24 individuals were included in this study, with 15 volunteers (62.5%) having originally received an mRNA vaccine and 9 (37.5%) an adenovirus vector vaccine. We found that 84 gene sets were differentially expressed in PBMCs from the two vaccine groups following <em>ex-vivo</em> secondary stimulation. Although cell populations did not significantly differ, pro-inflammatory cytokine responses to most stimuli were consistently higher in the adenovirus group compared to the mRNA group. These differences decreased after an mRNA booster vaccine.</div></div><div><h3>Discussion</h3><div>Our study findings provide additional support to the hypothesis that mRNA- and adenovirus-based vaccines differ in their broad immunological effects. Specifically, our observation that adenovirus-based vaccination tends to result in higher pro-inflammatory cytokine responses might help explain the difference in the heterologous effects of the two types of vaccines. Knowledge about NSEs is increasingly important for making public health and policy decisions, particularly for vulnerable populations.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105038"},"PeriodicalIF":3.3000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0008874925001248","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/10/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

The mRNA- and adenovirus-based COVID-19 vaccines may induce different heterologous effects on non-COVID morbidity. We aimed to investigate immunological mechanisms that may account for these differences.

Methods

We selected a subgroup of individuals from the TACTIC trial who had completed their COVID-19 vaccination scheme before the introduction of a BNT162b2 booster vaccine. Transcriptional activity, distribution of cell types and cytokine secretion were compared between those who were originally vaccinated with the adenovirus vaccine ChAdOx1-S, and those who had received the mRNA vaccine BNT162b2. Additionally, we investigated how these differences evolved after administration of a BNT162b2 booster vaccine.

Results

24 individuals were included in this study, with 15 volunteers (62.5%) having originally received an mRNA vaccine and 9 (37.5%) an adenovirus vector vaccine. We found that 84 gene sets were differentially expressed in PBMCs from the two vaccine groups following ex-vivo secondary stimulation. Although cell populations did not significantly differ, pro-inflammatory cytokine responses to most stimuli were consistently higher in the adenovirus group compared to the mRNA group. These differences decreased after an mRNA booster vaccine.

Discussion

Our study findings provide additional support to the hypothesis that mRNA- and adenovirus-based vaccines differ in their broad immunological effects. Specifically, our observation that adenovirus-based vaccination tends to result in higher pro-inflammatory cytokine responses might help explain the difference in the heterologous effects of the two types of vaccines. Knowledge about NSEs is increasingly important for making public health and policy decisions, particularly for vulnerable populations.

查看原文本刊更多论文

ChAdOx1-S和BNT162b2疫苗诱导的异源免疫效应

背景：基于mRNA和腺病毒的COVID-19疫苗可能对非COVID-19发病率产生不同的异源效应。我们的目的是研究可能解释这些差异的免疫学机制。方法：我们从战术试验中选择了一组在引入BNT162b2加强疫苗之前完成COVID-19疫苗接种计划的个体。比较了最初接种腺病毒疫苗ChAdOx1-S和mRNA疫苗BNT162b2的转录活性、细胞类型分布和细胞因子分泌情况。此外，我们研究了在接种BNT162b2加强疫苗后这些差异是如何演变的。结果：本研究纳入了24人，其中15名志愿者（62.5%）最初接种了mRNA疫苗，9名志愿者（37.5%）接种了腺病毒载体疫苗。我们发现，在离体二次刺激后，来自两个疫苗组的pbmc中有84组基因组存在差异表达。虽然细胞群没有显著差异，但与mRNA组相比，腺病毒组对大多数刺激的促炎细胞因子反应始终较高。这些差异在mRNA增强疫苗后减少。讨论：我们的研究结果为基于mRNA的疫苗和基于腺病毒的疫苗在其广泛的免疫效果上不同的假设提供了额外的支持。具体来说，我们观察到基于腺病毒的疫苗接种倾向于导致更高的促炎细胞因子反应，这可能有助于解释两种类型疫苗的异源效应差异。对于公共卫生和政策决策的制定，特别是对弱势群体而言，关于国家社会安全措施的知识越来越重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cellular immunology 生物-免疫学

CiteScore

8.20

自引率

2.30%

发文量

102

审稿时长

30 days

期刊介绍： Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.