Potent neutralization of SARS-CoV-2 including variants of concern by vaccines presenting the receptor-binding domain multivalently from nanoscaffolds,Bioengineering & Translational Medicine

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Potent neutralization of SARS-CoV-2 including variants of concern by vaccines presenting the receptor-binding domain multivalently from nanoscaffolds
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2021-08-27 , DOI: 10.1002/btm2.10253
Peter J Halfmann ₁ , Ana Castro ₂ , Kathryn Loeffler ₂ , Steven J Frey ₂ , Shiho Chiba ₁ , Yoshihiro Kawaoka _{1,

3,

4} , Ravi S Kane ₂

Affiliation

The persistence of the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought to the forefront the need for safe and effective vaccination strategies. In particular, the emergence of several variants with greater infectivity and resistance to current vaccines has motivated the development of a vaccine that elicits a broadly neutralizing immune response against all variants. In this study, we used a nanoparticle-based vaccine platform for the multivalent display of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein, the primary target of neutralizing antibodies. Multiple copies of RBD were conjugated to the SpyCatcher-mi3 protein nanoparticle to produce a highly immunogenic nanoparticle-based vaccine. RBD-SpyCatcher-mi3 vaccines elicited broadly cross-reactive antibodies that recognized the spike proteins of not just an early isolate of SARS-CoV-2, but also three SARS-CoV-2 variants of concern as well as SARS-CoV-1. Moreover, immunization elicited high neutralizing antibody titers against an early isolate of SARS-CoV-2 as well as four variants of concern, including the delta variant. These results reveal the potential of RBD-SpyCatcher-mi3 as a broadly protective vaccination strategy.

中文翻译：

通过纳米支架多价呈现受体结合结构域的疫苗有效中和 SARS-CoV-2，包括所关注的变体

全球严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 大流行的持续存在，使安全有效的疫苗接种策略的需求凸显出来。特别是，几种具有更强传染性和对现有疫苗具有更强抵抗力的变体的出现，促使人们开发出一种疫苗，该疫苗能够引发针对所有变体的广泛中和免疫反应。在这项研究中，我们使用基于纳米颗粒的疫苗平台来多价展示 SARS-CoV-2 刺突 (S) 蛋白的受体结合域 (RBD)，这是中和抗体的主要目标。RBD 的多个拷贝与 SpyCatcher-mi3 蛋白纳米颗粒缀合，以产生基于纳米颗粒的高免疫原性疫苗。RBD-SpyCatcher-mi3 疫苗引发了广泛的交叉反应抗体，这些抗体不仅可以识别 SARS-CoV-2 早期分离株的刺突蛋白，还可以识别三种值得关注的 SARS-CoV-2 变体以及 SARS-CoV-1。此外，免疫接种引发了针对 SARS-CoV-2 早期分离株以及四种受关注变体（包括 delta 变体）的高中和抗体滴度。这些结果揭示了 RBD-SpyCatcher-mi3 作为广泛保护性疫苗接种策略的潜力。

更新日期：2021-09-23

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