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表达 COBRA 血凝素的灭活流感病毒疫苗诱导产生广泛反应性、长寿命的保护性抗体。

Inactivated influenza virus vaccines expressing COBRA hemagglutinin elicited broadly reactive, long-lived protective antibodies.

机构信息

Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA.

Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, USA.

出版信息

Hum Vaccin Immunother. 2024 Dec 31;20(1):2356269. doi: 10.1080/21645515.2024.2356269. Epub 2024 Jun 2.


DOI:10.1080/21645515.2024.2356269
PMID:38826029
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11152115/
Abstract

The influenza viruses cause seasonal respiratory illness that affect millions of people globally every year. Prophylactic vaccines are the recommended method to prevent the breakout of influenza epidemics. One of the current commercial influenza vaccines consists of inactivated viruses that are selected months prior to the start of a new influenza season. In many seasons, the vaccine effectiveness (VE) of these vaccines can be relatively low. Therefore, there is an urgent need to develop an improved, more universal influenza vaccine (UIV) that can provide broad protection against various drifted strains in all age groups. To meet this need, the computationally optimized broadly reactive antigen (COBRA) methodology was developed to design a hemagglutinin (HA) molecule as a new influenza vaccine. In this study, COBRA HA-based inactivated influenza viruses (IIV) expressing the COBRA HA from H1 or H3 influenza viruses were developed and characterized for the elicitation of immediate and long-term protective immunity in both immunologically naïve or influenza pre-immune animal models. These results were compared to animals vaccinated with IIV vaccines expressing wild-type H1 or H3 HA proteins (WT-IIV). The COBRA-IIV elicited long-lasting broadly reactive antibodies that had hemagglutination-inhibition (HAI) activity against drifted influenza variants.

摘要

流感病毒每年都会引起全球数百万人的季节性呼吸道疾病。预防性疫苗是预防流感爆发的推荐方法。目前的一种商业流感疫苗由在新流感季节开始前几个月选择的灭活病毒组成。在许多季节,这些疫苗的疫苗有效性(VE)可能相对较低。因此,迫切需要开发一种改进的、更通用的流感疫苗(UIV),为所有年龄段的各种漂移株提供广泛的保护。为了满足这一需求,开发了计算优化的广泛反应性抗原(COBRA)方法来设计血凝素(HA)分子作为一种新的流感疫苗。在这项研究中,开发了基于 COBRA HA 的灭活流感病毒(IIV),表达来自 H1 或 H3 流感病毒的 COBRA HA,并在免疫原性未成熟或流感预先免疫的动物模型中对其诱导即时和长期保护免疫进行了表征。将这些结果与用表达野生型 H1 或 H3 HA 蛋白的 IIV 疫苗(WT-IIV)接种的动物进行了比较。COBRA-IIV 诱导了持久的广泛反应性抗体,这些抗体具有针对漂移流感变体的血凝抑制(HAI)活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/4f21e01ccb8c/KHVI_A_2356269_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/81f87d6f6143/KHVI_A_2356269_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/3756bdf8a42f/KHVI_A_2356269_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/689a18481448/KHVI_A_2356269_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/0a9d79659fb2/KHVI_A_2356269_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/4ba95d3dab3c/KHVI_A_2356269_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/4f21e01ccb8c/KHVI_A_2356269_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/81f87d6f6143/KHVI_A_2356269_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/3756bdf8a42f/KHVI_A_2356269_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/689a18481448/KHVI_A_2356269_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/0a9d79659fb2/KHVI_A_2356269_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/4ba95d3dab3c/KHVI_A_2356269_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e867/11152115/4f21e01ccb8c/KHVI_A_2356269_F0006_OC.jpg

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Inactivated influenza virus vaccines expressing COBRA hemagglutinin elicited broadly reactive, long-lived protective antibodies.

Hum Vaccin Immunother. 2024-12-31

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引用本文的文献

[1]
COVID-19 Vaccination Enhances the Immunogenicity of Seasonal Influenza Vaccination in the Elderly.

Vaccines (Basel). 2025-5-16

[2]
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J Immunol. 2025-7-1

[3]
Multivalent H3 COBRA-based influenza vaccine elicits enhanced immune response in a pre-immune elderly ferret model.

Vaccine. 2025-5-22

[4]
A single dose of inactivated influenza virus vaccine expressing COBRA hemagglutinin elicits broadly-reactive and long-lasting protection.

PLoS One. 2025-2-21

[5]
Development of broadly protective influenza B vaccines.

NPJ Vaccines. 2025-1-7

本文引用的文献

[1]
Kinetic of the Antibody Response Following AddaVax-Adjuvanted Immunization with Recombinant Influenza Antigens.

Vaccines (Basel). 2022-8-14

[2]
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Hum Vaccin Immunother. 2022-11-30

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Bivalent H1 and H3 COBRA Recombinant Hemagglutinin Vaccines Elicit Seroprotective Antibodies against H1N1 and H3N2 Influenza Viruses from 2009 to 2019.

J Virol. 2022-4-13

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