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一种变异纳米颗粒疫苗的免疫原性和保护作用，该疫苗能针对 SARS-CoV-2 变体提供广泛的中和作用。

Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants.

机构信息

The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Center for Pathogen Research, The University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

出版信息

Nat Commun. 2023 Feb 28;14(1):1130. doi: 10.1038/s41467-022-35606-6.

DOI:10.1038/s41467-022-35606-6
PMID:36854666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9972327/
Abstract

SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351, and Omicron/BA.1. Mice vaccinated with two doses of Novavax prototype NVX-CoV2373 (rS-WU1) or rS-Beta alone, in combination, or heterologous prime-boost, are protected from challenge. Virus titer is undetectable in lungs in all vaccinated mice, and Th1-skewed cellular responses are observed. We tested sera from a panel of variant spike protein vaccines and find broad neutralization and inhibition of spike:ACE2 binding from the rS-Beta and rS-Delta vaccines against a variety of variants including Omicron. This study demonstrates that rS-Beta vaccine alone or in combination with rS-WU1 induces antibody-and cell-mediated responses that are protective against challenge with SARS-CoV-2 variants and offers broader neutralizing capacity than a rS-WU1 prime/boost regimen alone. Together, these nonhuman primate and murine data suggest a Beta variant booster dose could elicit a broad immune response to fight new and future SARS-CoV-2 variants.

摘要

SARS-CoV-2 变体的传播能力增强，对已接种疫苗的个体的感染风险也更高。我们证明，一种基于 Beta/B.1.351（rS-Beta）的重组前融合稳定 Spike（rS）蛋白疫苗，在接种 NVX-CoV2373 疫苗一年后作为加强针使用时，能够在食蟹猴中产生针对 SARS-CoV-2 变体的强大记忆应答。此外，rS-Beta 在小鼠中具有高度免疫原性，能够产生针对 WA1/2020、Beta/B.1.351 和 Omicron/BA.1 的中和抗体。用两剂 Novavax 原型 NVX-CoV2373（rS-WU1）或 rS-Beta 单独、联合或异源初免-加强免疫接种的小鼠，能够免受挑战。所有接种疫苗的小鼠肺部的病毒滴度均无法检测到，并且观察到 Th1 偏向的细胞反应。我们测试了一组变体 Spike 蛋白疫苗的血清，发现 rS-Beta 和 rS-Delta 疫苗对包括 Omicron 在内的多种变体具有广泛的中和作用，并抑制 Spike:ACE2 结合。这项研究表明，rS-Beta 疫苗单独或与 rS-WU1 联合使用，可诱导针对 SARS-CoV-2 变体的抗体和细胞介导的保护性应答，并提供比 rS-WU1 初免-加强方案更广泛的中和能力。这些非人类灵长类动物和小鼠数据表明，Beta 变体加强剂量可以引发广泛的免疫反应，以对抗新的和未来的 SARS-CoV-2 变体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/e25b39bda1c2/41467_2022_35606_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/2a1bba7a871a/41467_2022_35606_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/1be2c9dc14ec/41467_2022_35606_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/4bab4a736e65/41467_2022_35606_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/38ee97ffe2b6/41467_2022_35606_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/0dc1b5d29069/41467_2022_35606_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/e25b39bda1c2/41467_2022_35606_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/2a1bba7a871a/41467_2022_35606_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/1be2c9dc14ec/41467_2022_35606_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/4bab4a736e65/41467_2022_35606_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/38ee97ffe2b6/41467_2022_35606_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/0dc1b5d29069/41467_2022_35606_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/9974983/e25b39bda1c2/41467_2022_35606_Fig6_HTML.jpg

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