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鼻内接种小儿副流感病毒载体 SARS-CoV-2 疫苗可保护猴子。

Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in monkeys.

机构信息

RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Cell. 2022 Dec 8;185(25):4811-4825.e17. doi: 10.1016/j.cell.2022.11.006. Epub 2022 Nov 10.


DOI:10.1016/j.cell.2022.11.006
PMID:36423629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9684001/
Abstract

Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza-virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal immunoglobulin A (IgA) and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern of alpha, beta, and delta lineages, while their ability to neutralize Omicron sub-lineages was lower. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4 and CD8 T cell responses, including tissue-resident memory cells in the lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.

摘要

需要在呼吸道和全身都能引发免疫的儿科 SARS-CoV-2 疫苗。我们在正在临床开发的小儿副流感病毒疫苗的基础上,生成了一种表达 SARS-CoV-2 预融合稳定 Spike(S)蛋白的活减毒副流感病毒载体候选疫苗(B/HPIV3/S-6P),并在恒河猴中评估了其免疫原性和保护效力。单次鼻内/气管内剂量的 B/HPIV3/S-6P 可诱导强烈的 S 特异性气道黏膜免疫球蛋白 A(IgA)和 IgG 应答。还在血清中诱导了高水平的 S 特异性抗体,这些抗体能有效地中和α、β和δ谱系的 SARS-CoV-2 变体,而对奥密克戎亚谱系的中和能力较低。此外,B/HPIV3/S-6P 诱导了强烈的全身和肺部 S 特异性 CD4 和 CD8 T 细胞应答,包括肺部的组织驻留记忆细胞。在攻毒后,免疫猴的呼吸道和肺部组织中均无法检测到 SARS-CoV-2 复制。B/HPIV3/S-6P 将作为儿科鼻内 SARS-CoV-2/副流感病毒 3 疫苗进行临床评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/929220e521be/figs4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/684b61675412/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/9c2ebc6d24e8/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/a4bcce7192fa/figs1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/0b4826089f1d/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/9a2380e2c63d/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/41c2d0c43caf/figs2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/f8b2a57e1ca4/figs3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/59ff0499399f/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/235496c2eb92/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/929220e521be/figs4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/684b61675412/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/9c2ebc6d24e8/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/a4bcce7192fa/figs1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/0b4826089f1d/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/9a2380e2c63d/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/41c2d0c43caf/figs2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/f8b2a57e1ca4/figs3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/59ff0499399f/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/235496c2eb92/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d5/9684001/929220e521be/figs4_lrg.jpg

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PLoS Pathog. 2025-4-21

[5]
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J Virol. 2025-4-15

[6]
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[7]
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[10]
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本文引用的文献

[1]
Vaccine protection against the SARS-CoV-2 Omicron variant in macaques.

Cell. 2022-4-28

[2]
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A single intranasal dose of a live-attenuated parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in hamsters.

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Science. 2021-11-19

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Mucosal Immunol. 2022-3

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Sci Immunol. 2021-11-19

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