Adeleke Richard A, Sahler Julie, Choi Annette, Roth Kyle, Upadhye Viraj, Ezzatpour Shahrzad, Imbiakha Brian, Khomandiak Solomiia, Diaz Annika, Whittaker Gary R, Jager Mason C, August Avery, Buchholz David W, Aguilar Hector C
Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
Department of Population Medicine and Diagnostic Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
Sci Adv. 2025 Jan 31;11(5):eadq4545. doi: 10.1126/sciadv.adq4545. Epub 2025 Jan 29.
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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）和流感病毒可导致人类严重的呼吸系统疾病和死亡，在有基础健康问题的个体中情况会加剧，仍然是全球重大的公共卫生问题。在此，我们开发了一种双价复制缺陷型单周期假型水疱性口炎病毒疫苗，它包含一种缺乏弗林蛋白酶切割位点的预融合稳定型SARS-CoV-2刺突蛋白和一种全长甲型流感病毒神经氨酸酶蛋白。用该疫苗接种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，并在受到任一病毒攻击时预防发病和死亡。此外，该疫苗在用不同的流感病毒株攻击时提供了异源保护，支持了使用神经氨酸酶来增加疫苗保护广度的优势。目前，尚无针对SARS-CoV-2和流感病毒的双价疫苗被批准使用。我们的研究支持利用这一平台开发针对多种病毒的安全有效疫苗。
