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基于 RBD 偶联灭活甲型流感病毒的 SARS-CoV-2 和流感双重打击疫苗。

A SARS-CoV-2 and influenza double hit vaccine based on RBD-conjugated inactivated influenza A virus.

机构信息

Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA.

Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and North Carolina State University, Raleigh, NC 27606, USA.

出版信息

Sci Adv. 2023 Jun 23;9(25):eabo4100. doi: 10.1126/sciadv.abo4100.

DOI:10.1126/sciadv.abo4100
PMID:37352360
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10289656/
Abstract

The circulating flu viruses merging with the ongoing COVID-19 pandemic raises a more severe threat that promotes the infectivity of SARS-CoV-2 associated with higher mortality rates. Here, we conjugated recombinant receptor binding domain (RBD) of SARS-CoV-2 spike protein onto inactivated influenza A virus (Flu) to develop a SARS-CoV-2 virus-like particle (VLP) vaccine with two-hit protection. This double-hit vaccine (Flu-RBD) not only induced protective immunities against SARS-CoV-2 but also remained functional as a flu vaccine. The Flu core improved the retention and distribution of Flu-RBD vaccine in the draining lymph nodes, with enhanced immunogenicity. In a hamster model of live SARS-CoV-2 infection, two doses of Flu-RBD efficiently protected animals against viral infection. Furthermore, Flu-RBD VLP elicited a strong neutralization activity against both SARS-CoV-2 Delta pseudovirus and wild-type influenza A H1N1 inactivated virus in mice. Overall, the Flu-RBD VLP vaccine is a promising candidate for combating COVID-19, influenza A, and coinfection.

摘要

循环的流感病毒与持续的 COVID-19 大流行合并在一起，带来了更严重的威胁，增加了与更高死亡率相关的 SARS-CoV-2 的传染性。在这里，我们将 SARS-CoV-2 刺突蛋白的重组受体结合域（RBD）缀合到已灭活的流感 A 病毒（流感）上，开发了一种具有双效保护作用的 SARS-CoV-2 病毒样颗粒（VLP）疫苗。这种双效疫苗（流感-RBD）不仅诱导了针对 SARS-CoV-2 的保护性免疫，而且仍然可以作为流感疫苗发挥作用。流感核心增强了 Flu-RBD 疫苗在引流淋巴结中的保留和分布，提高了免疫原性。在活 SARS-CoV-2 感染的仓鼠模型中，两剂 Flu-RBD 能够有效地保护动物免受病毒感染。此外，Flu-RBD VLP 在小鼠中对 SARS-CoV-2 Delta 假病毒和野生型甲型 H1N1 流感灭活病毒均表现出强烈的中和活性。总的来说，Flu-RBD VLP 疫苗是一种有前途的对抗 COVID-19、流感 A 和合并感染的候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/08201f459987/sciadv.abo4100-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/10c6b2611813/sciadv.abo4100-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/a057ef59a5e9/sciadv.abo4100-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/ca7fa725ed64/sciadv.abo4100-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/05d7563ad2bc/sciadv.abo4100-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/9d7d8bee6d34/sciadv.abo4100-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/f21a786816fa/sciadv.abo4100-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/08201f459987/sciadv.abo4100-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/10c6b2611813/sciadv.abo4100-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/a057ef59a5e9/sciadv.abo4100-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/ca7fa725ed64/sciadv.abo4100-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/05d7563ad2bc/sciadv.abo4100-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/9d7d8bee6d34/sciadv.abo4100-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/f21a786816fa/sciadv.abo4100-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4842/10289656/08201f459987/sciadv.abo4100-f7.jpg

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[8]
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本文引用的文献

[1]
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J Infect Public Health. 2023-2

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