One dose of COVID-19 nanoparticle vaccine REVC-128 protects against SARS-CoV-2 challenge at two weeks post-immunization

A COVID-19 vaccine that can give early protection is needed to eliminate the viral spread efficiently. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomains with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titre at two weeks post-immunization. This is significantly higher than titre caused by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by a spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for the SARS-CoV-2 virus challenge was implemented two weeks post a single dose of REVC-128 immunization. The results showed that vaccination protects hamsters against the SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage for protected animals, compared with ∼10% weight loss, high viral loads and tissue damage in unprotected animals. Furthermore, the data showed that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine to give the earliest protection against SARS-CoV-2 infection.

为高效阻断新冠病毒传播，亟需一款可提供早期保护效力的COVID-19疫苗。本研究成功开发了一款纳米颗粒候选疫苗REVC-128：将位点614带有甘氨酸（Glycine, G）的三聚体刺突蛋白胞外域多聚化组装至纳米颗粒载体之上。该疫苗的体外表征实验证实其结构与抗原完整性完好。小鼠体内免疫原性评价结果显示，单剂接种该疫苗后两周即可诱导出强效的血清中和抗体滴度，该滴度显著高于未组装于纳米颗粒载体的三聚体刺突蛋白所诱导的抗体滴度。对比接种纳米颗粒组装/未组装刺突蛋白的动物血清与刺突蛋白亚基的结合情况，结果显示纳米颗粒载体更倾向于展示刺突蛋白受体结合域（Receptor-Binding Domain, RBD）而非S2亚基，这可能使其诱导的抗体反应中和性更强，但交叉反应性更弱。此外，本研究在单剂REVC-128免疫两周后，采用叙利亚金黄仓鼠建立了SARS-CoV-2病毒攻毒体内模型。结果显示，疫苗接种可使仓鼠抵御SARS-CoV-2病毒攻毒：与未接种组动物约10%的体重下降、高病毒载量及组织损伤相比，接种组动物体重保持稳定、病毒载量受到抑制且组织损伤得以缓解。此外，实验数据证实REVC-128疫苗在最高37℃条件下至少可保持4周热稳定性。结合蛋白疫苗已有的安全使用历史，上述研究结果表明，REVC-128是一款安全、稳定且高效的单剂疫苗，可为机体提供针对SARS-CoV-2感染的早期保护。