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早期黏膜事件促进活减毒流感疫苗产生独特的黏膜和系统抗体应答。

Early mucosal events promote distinct mucosal and systemic antibody responses to live attenuated influenza vaccine.

机构信息

National Heart and Lung Institute, Imperial College London, London, UK.

Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.

出版信息

Nat Commun. 2023 Dec 5;14(1):8053. doi: 10.1038/s41467-023-43842-7.

DOI:10.1038/s41467-023-43842-7
PMID:38052824
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10697962/
Abstract

Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8 and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.

摘要

与肌肉内疫苗相比，鼻内给药疫苗具有诱导局部黏膜免疫应答的优势，这可能阻止感染并中断呼吸道病原体的传播。减毒活流感疫苗（LAIV）在预防儿童流感方面有效，但 LAIV 的保护相关因素仍不清楚。在对年轻成年志愿者进行研究时，我们观察到 LAIV 在黏膜和血液中诱导出独特的、分隔的抗体应答。为了寻找这些独特抗体应答的免疫学相关因素，我们发现与接种后 8 小时内黏膜中 IL-33 的释放以及接种后 7 天出现的不同的 CD8 和循环滤泡辅助 T 细胞（cTfh）应答相关。黏膜抗体与血液抗体分别诱导，与接种后早期的独特免疫应答相关，并且可能为黏膜疫苗接种提供保护相关因素。本研究在 NCT04110366 注册，并报告了主要（黏膜抗体）和次要（血液抗体以及鼻内病毒载量和细胞因子）终点数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/7b873a5b0443/41467_2023_43842_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/af28119dd59a/41467_2023_43842_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/4fb208154065/41467_2023_43842_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/eea73ecb92f3/41467_2023_43842_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/684158ad668e/41467_2023_43842_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/7b873a5b0443/41467_2023_43842_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/af28119dd59a/41467_2023_43842_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/93eb10c122ac/41467_2023_43842_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/e30affae40d1/41467_2023_43842_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/4fb208154065/41467_2023_43842_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/eea73ecb92f3/41467_2023_43842_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/684158ad668e/41467_2023_43842_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ba/10697962/7b873a5b0443/41467_2023_43842_Fig7_HTML.jpg

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