Department of Molecular Genetics and Microbiology, Duke Universitygrid.26009.3dgrid.471396.e School of Medicine, Durham, North Carolina, USA.
Duke Human Vaccine Institute, Duke Universitygrid.26009.3dgrid.471396.e School of Medicine, Durham, North Carolina, USA.
J Virol. 2022 Aug 10;96(15):e0068922. doi: 10.1128/jvi.00689-22. Epub 2022 Jul 12.
Vaccines targeting SARS-CoV-2 have been shown to be highly effective; however, the breadth against emerging variants and the longevity of protection remains unclear. Postimmunization boosting has been shown to be beneficial for disease protection, and as new variants continue to emerge, periodic (and perhaps annual) vaccination will likely be recommended. New seasonal influenza virus vaccines currently need to be developed every year due to continual antigenic drift, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting both influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed an influenza A virus (IAV) genetic platform that allows the incorporation of an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicited neutralizing antibodies and provided protection from lethal challenge with both pathogens in mice. This approach may allow the leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses. The rapid emergence of SARS-CoV-2 variants since the onset of the pandemic has highlighted the need for both periodic vaccination "boosts" and a platform that can be rapidly reformulated to manufacture new vaccines. In this work, we report an approach that can utilize current influenza vaccine manufacturing infrastructure to generate combination vaccines capable of protecting from both influenza virus- and SARS-CoV-2-induced disease. The production of a combined influenza/SARS-CoV-2 vaccine may represent a practical solution to boost immunity to these important respiratory viruses without the increased cost and administration burden of multiple independent vaccines.
针对 SARS-CoV-2 的疫苗已被证明具有高度有效性;然而,针对新兴变体的广度和保护的持久性仍不清楚。免疫后增强已被证明对疾病保护有益,随着新变体的不断出现,定期(可能是每年)接种疫苗可能会被推荐。由于持续的抗原漂移,新的季节性流感病毒疫苗每年都需要开发,这一任务得益于强大的全球疫苗生产和分发基础设施。为了开发一种既能针对流感病毒又能针对 SARS-CoV-2 的季节性组合疫苗,且易于频繁进行配方更改,我们开发了一种流感病毒 A (IAV) 基因平台,该平台允许将 SARS-CoV-2 刺突 (S) 蛋白的免疫原性结构域整合到 IAV 颗粒上。用这种组合疫苗接种可引发中和抗体,并为小鼠提供针对两种病原体的致命性攻击的保护。这种方法可能允许利用现有的流感疫苗基础设施来为流感和冠状病毒生成一种具有成本效益且可扩展的季节性疫苗解决方案。自大流行开始以来,SARS-CoV-2 变体的快速出现突出表明,需要定期进行疫苗“增强”,并需要一个能够快速重新配方以制造新疫苗的平台。在这项工作中,我们报告了一种方法,该方法可以利用当前的流感疫苗制造基础设施来生产能够预防流感病毒和 SARS-CoV-2 引起的疾病的组合疫苗。联合流感/ SARS-CoV-2 疫苗的生产可能是一种实用的解决方案,可以增强对这些重要呼吸道病毒的免疫力,而不会增加多种独立疫苗的成本和管理负担。