Replication-incompetent VSV-based vaccine elicits protective responses against SARS-CoV-2 and influenza virus

IF 12.5 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Advances Pub Date : 2025-01-29 DOI:10.1126/sciadv.adq4545
Richard A. Adeleke, Julie Sahler, Annette Choi, Kyle Roth, Viraj Upadhye, Shahrzad Ezzatpour, Brian Imbiakha, Solomiia Khomandiak, Annika Diaz, Gary R. Whittaker, Mason C. Jager, Avery August, David W. Buchholz, Hector C. Aguilar
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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses lead to severe respiratory illnesses and death in humans, exacerbated in individuals with underlying health conditions, remaining substantial global public health concerns. Here, we developed a bivalent replication-incompetent single-cycle pseudotyped vesicular stomatitis virus vaccine that incorporates both a prefusion-stabilized SARS-CoV-2 spike protein lacking a furin cleavage site and a full-length influenza A virus neuraminidase protein. Vaccination of K18-hACE2 or C57BL/6J mouse models generated durable levels of neutralizing antibodies, T cell responses, and protection from morbidity and mortality upon challenge with either virus. Furthermore, the vaccine provided heterologous protection upon challenge with a different influenza virus strain, supporting the advantage of using NA to increase the breadth of vaccine protection. Now, no bivalent vaccine is approved for use against both SARS-CoV-2 and influenza virus. Our study supports using this platform to develop safe and efficient vaccines against multiple viruses.

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基于无复制能力vsv的疫苗可引起针对SARS-CoV-2和流感病毒的保护性反应。
严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2)和流感病毒导致人类严重呼吸道疾病和死亡,对有潜在健康问题的个体来说,情况会加剧,这仍然是重大的全球公共卫生问题。在这里,我们开发了一种双价复制能力不强的单周期伪水疱性口炎病毒疫苗,该疫苗结合了缺乏furin切割位点的预灌注稳定的SARS-CoV-2刺突蛋白和全长甲型流感病毒神经氨酸酶蛋白。接种K18-hACE2或C57BL/6J小鼠模型可产生持久水平的中和抗体、T细胞反应,并保护其免受任一病毒攻击时的发病率和死亡率。此外,该疫苗在不同流感病毒株的攻击下提供异源保护,支持使用NA增加疫苗保护广度的优势。现在,没有一种双价疫苗被批准用于同时对抗SARS-CoV-2和流感病毒。我们的研究支持利用这个平台开发针对多种病毒的安全有效的疫苗。
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来源期刊
Science Advances
Science Advances 综合性期刊-综合性期刊
CiteScore
21.40
自引率
1.50%
发文量
1937
审稿时长
29 weeks
期刊介绍: Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.
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