mRNA和腺病毒载体SARS-CoV-2疫苗诱导的免疫反应对CD4 T细胞辅助的不同要求。

Distinct Requirements for CD4 T Cell Help for Immune Responses Induced by mRNA and Adenovirus-Vector SARS-CoV-2 Vaccines.

作者信息

Yong Lyn, Hutchings Claire, Barnes Eleanor, Klenerman Paul, Provine Nicholas M

机构信息

Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine-Experimental Medicine, University of Oxford, Oxford, UK.

出版信息

Eur J Immunol. 2025 Jan;55(1):e202451142. doi: 10.1002/eji.202451142. Epub 2024 Nov 27.

Abstract

CD4 T cells have been established as central orchestrators of cellular and humoral immune responses to infection or vaccination. However, the need for CD4 T cell help to generate primary CD8 T cell responses is variable depending on the infectious agent or vaccine and yet consistently required for the recall of CD8 T cell memory responses or antibody responses. Given the deployment of new vaccine platforms such as nucleoside-modified mRNA vaccines, we sought to elucidate the requirement for CD4 T cell help in the induction of cellular and antibody responses to mRNA and adenovirus (Ad)-vectored vaccines against SARS-CoV-2. Using antibody-mediated depletion of CD4 T cells in a mouse immunization model, we observed that CD4 T cell help was dispensable for both primary and secondary CD8 T cell responses to the BNT162b2 and mRNA-1273 mRNA vaccines but required for the AZD1222 Ad-vectored vaccine. Nonetheless, CD4 T cell help was needed by both mRNA and Ad-vectored vaccine platforms for the generation of antibodies, demonstrating the centrality of CD4 T cells in vaccine-induced protective immunity against SARS-CoV-2. Ultimately, this highlights the shared and distinct regulation of humoral and cellular responses induced by these vaccine platforms.

摘要

CD4 T细胞已被确立为针对感染或疫苗接种的细胞免疫和体液免疫反应的核心协调者。然而,产生初始CD8 T细胞反应所需的CD4 T细胞辅助因感染因子或疫苗而异,但对于CD8 T细胞记忆反应或抗体反应的再次激活始终是必需的。鉴于新型疫苗平台如核苷修饰的mRNA疫苗的应用,我们试图阐明在诱导针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的mRNA和腺病毒(Ad)载体疫苗的细胞反应和抗体反应中对CD4 T细胞辅助的需求。在小鼠免疫模型中使用抗体介导的CD4 T细胞耗竭方法,我们观察到,对于BNT162b2和mRNA-1273 mRNA疫苗的初始和二次CD8 T细胞反应,CD4 T细胞辅助是可有可无的,但对于AZD1222 Ad载体疫苗则是必需的。尽管如此,mRNA和Ad载体疫苗平台产生抗体都需要CD4 T细胞辅助,这表明CD4 T细胞在疫苗诱导的针对SARS-CoV-2的保护性免疫中具有核心作用。最终,这突出了这些疫苗平台诱导的体液反应和细胞反应的共同和独特调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eeb/11739681/7d6d423e9583/EJI-55-e202451142-g002.jpg

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