Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice.
Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice.
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DOI：
10.1016/j.jvacx.2021.100126
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发表时间：
2021-11-05
期刊：
影响因子：
3.8
通讯作者：
Lehrer AT
中科院分区：
文献类型：
--
作者：
Lai CY;To A;Ann S Wong T;Lieberman MM;Clements DE;Senda JT;Ball AH;Pessaint L;Andersen H;Furuyama W;Marzi A;Donini O;Lehrer AT
几种COVID-19疫苗从概念到获得FDA和EMA批准紧急使用的速度是疫苗开发史上无与伦比的成就。目前正在进行使用高效疫苗的大规模疫苗接种工作，以产生足够的群体免疫力，减少SARS-CoV-2病毒的传播。尽管有最先进的疫苗技术，但全球接受者的覆盖率，特别是在资源贫乏地区，仍然是一个挑战，因为未接种过疫苗的人群中的遗传漂变威胁到疫苗的整体效力。在这项研究中，我们描述了昆虫细胞表达的SARS-CoV-2刺突蛋白胞外结构域构建体的生产，并在小鼠中检测其免疫原性。我们证明，当与CoVaccine HTTM佐剂（一种与冻干相容的水包油纳米乳剂）一起配制时，我们的候选疫苗引发广谱IgG应答，针对SARS-CoV-2原型和相关变体（特别是B.1.351（Beta）和P.1）的高中和抗体（NtAb）滴度。（γ），和抗原特异性IFN-γ分泌应答。值得注意的是，不同的胞外域构建体产生针对原型菌株和一些VOC的NtAb滴度的变化。剂量反应实验表明，NtAb滴度随抗原剂量而增加，但不随佐剂剂量而增加，并且在较低的佐剂剂量下可能更高。我们的研究结果奠定了免疫学基础的干热稳定的疫苗，无需冷藏部署的发展。
The speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain constructs and examined their immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HTTM adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody (NtAb) titers against SARS-CoV-2 prototype and variants of concern, specifically B.1.351 (Beta) and P.1. (Gamma), and an antigen-specific IFN-γ secreting response in outbred mice. Of note, different ectodomain constructs yielded variations in NtAb titers against the prototype strain and some VOC. Dose response experiments indicated that NtAb titers increased with antigen dose, but not adjuvant dose, and may be higher with a lower adjuvant dose. Our findings lay the immunological foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.
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影响因子：
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