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黏膜型腺病毒疫苗加强免疫可诱导 IgA 产生，并可持久预防非人灵长类动物感染 XBB.1.16。

Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates.

机构信息

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Department of Pediatrics, Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.

出版信息

Nat Immunol. 2024 Oct;25(10):1913-1927. doi: 10.1038/s41590-024-01951-5. Epub 2024 Sep 3.

DOI:10.1038/s41590-024-01951-5
PMID:39227514
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11436372/
Abstract

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1-BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2.

摘要

黏膜途径的疫苗接种可以在感染部位预防严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的复制，并限制传播。我们比较了在非人类灵长类动物（NHPs）中，肌肉内加强免疫双价 mRNA 编码 WA1 和 BA.5 刺突蛋白或黏膜加强免疫用 WA1-BA.5 双价 chimpanzee 腺病毒载体疫苗通过鼻内或气溶胶装置接种后，对异源 XBB.1.16 挑战的保护作用。通过黏膜途径加强免疫的 NHPs 分别在鼻腔和肺部的病毒复制最少。相比之下，肌肉内 mRNA 疫苗的保护作用仅限于下呼吸道。黏膜递送的疫苗可诱导持久的气道 IgG 和 IgA 反应，并且与肌肉内 mRNA 疫苗不同，可在肺部诱导针对刺突蛋白的 B 细胞。IgG、IgA 和 T 细胞反应与肺部的保护作用相关，而黏膜 IgA 与上呼吸道的保护作用相关。这项研究强调了黏膜和血清保护作用的差异，以及黏膜疫苗如何持久地预防 SARS-CoV-2 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/9997bcac7642/41590_2024_1951_Fig16_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/9997bcac7642/41590_2024_1951_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/f440598a9f32/41590_2024_1951_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/68f5c311abea/41590_2024_1951_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/bfc361424897/41590_2024_1951_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/604b1c6c9ffb/41590_2024_1951_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/79a30f16c572/41590_2024_1951_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/38fa83384593/41590_2024_1951_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/20c690223559/41590_2024_1951_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/fccd7a9a4f2d/41590_2024_1951_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/8f8f26bdfc6c/41590_2024_1951_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/0561e35b64f7/41590_2024_1951_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/2158c60bea7a/41590_2024_1951_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/c64071891856/41590_2024_1951_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/1ede0e90e0cc/41590_2024_1951_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/b225d8295d01/41590_2024_1951_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4a4/11436372/9997bcac7642/41590_2024_1951_Fig16_ESM.jpg

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本文引用的文献

[1]
Mucosal vaccine-induced cross-reactive CD8 T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection.

Nat Immunol. 2024-3

[2]
Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques.

Nature. 2024-2

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Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection.

Sci Adv. 2023-9-22

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Front Immunol. 2023

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NPJ Vaccines. 2023-5-10

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Lancet Microbe. 2023-7

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