Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice.
Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice.
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三价 NDV-HXP-S 疫苗可预防小鼠体内系统发育较远的 SARS-CoV-2 变异体。
DOI：
10.1101/2022.03.21.485247
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Kramm
中科院分区：
文献类型：
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作者：
González-Domínguez,Irene;Martínez,JoseLuis;Slamanig,Stefan;Lemus,Nicholas;Liu,Yonghong;Lai,TsoiYing;Carreño,JuanManuel;SinghA,Gagandeep;SinghB,Gagandeep;Schotsaert,Michael;Mena,Ignacio;McCroskery,Stephen;Coughlan,Lynda;Kramm
公平获得疫苗对于限制2019冠状病毒病（COVID-19）大流行和新型严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）变体的出现的全球影响是必要的。在先前的研究中，我们描述了一种低成本疫苗的开发，该疫苗基于表达来自SARS-CoV-2的融合前稳定的刺突蛋白的纽卡斯尔病病毒（NDV），命名为NDV-HXP-S。在这里，我们提出了下一代NDV-HXP-S变体疫苗的开发，该疫苗表达β、γ和δ变体的稳定刺突蛋白。在小鼠中测试二价、三价和四价制剂中的变体疫苗的组合的免疫原性和保护。我们表明，由祖先的武汉疫苗、贝塔疫苗和德尔塔疫苗组成的三价制剂，大大提高了对不匹配的、遗传学上遥远的变异体的保护水平和交叉中和抗体的水平，包括目前流行的Omicron变体。重要性这篇手稿描述了一项关于基于纽卡斯尔病病毒（NDV）的疫苗的扩展工作，重点是表达不同融合前-融合蛋白的NDV载体的多价制剂。不同SARS-CoV-2变异体（VOC）刺突蛋白的稳定版本。我们在这里证明，这种低成本的NDV平台可以很容易地适应于构建针对SARS-CoV-2变体的疫苗。重要的是，我们表明，由祖先的武汉，贝塔和德尔塔疫苗组成的三价制剂，大大提高了保护水平和交叉中和抗体对不匹配的，遗传学上遥远的变体，包括目前流行的Omicron变体。我们相信，这些发现将有助于指导未来针对新变种的大流行准备工作。
Equitable access to vaccines is necessary to limit the global impact of the coronavirus disease 2019 (COVID-19) pandemic and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In previous studies, we described the development of a low-cost vaccine based on a Newcastle Disease virus (NDV) expressing the prefusion-stabilized spike protein from SARS-CoV-2, named NDV-HXP-S. Here, we present the development of next-generation NDV-HXP-S variant vaccines, which express the stabilized spike protein of the Beta, Gamma, and Delta variants of concerns (VOC). Combinations of variant vaccines in bivalent, trivalent, and tetravalent formulations were tested for immunogenicity and protection in mice. We show that the trivalent preparation, composed of the ancestral Wuhan, Beta, and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant.IMPORTANCEThis manuscript describes an extended work on the Newcastle disease virus (NDV)-based vaccine focusing on multivalent formulations of NDV vectors expressing different prefusion-stabilized versions of the spike proteins of different SARS-CoV-2 variants of concern (VOC). We demonstrate here that this low-cost NDV platform can be easily adapted to construct vaccines against SARS-CoV-2 variants. Importantly, we show that the trivalent preparation, composed of the ancestral Wuhan, Beta, and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant. We believe that these findings will help to guide efforts for pandemic preparedness against new variants in the future.