Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 (COVID-19) pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2GΔHR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with the same potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2GΔHR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in mice. Compared with the soluble spike, the I3-01v9 SApNP showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold stronger germinal center reactions in lymph node follicles.

中文翻译：

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引发对 SARS-CoV-2 变体的广泛中和抗体反应的 COVID-19 纳米颗粒候选疫苗的机制

诱导针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 新变体产生有效中和抗体 (NAb) 反应的疫苗对于对抗 2019 年冠状病毒病 (COVID-19) 大流行至关重要。我们证明了由自组装蛋白纳米颗粒 (SApNPs) 诱导的小鼠血浆，其中存在 20 个合理设计的 S2GΔHR2 尖峰，可以中和 B.1.1.7、B.1.351、P.1 和 B .1.617 变体具有相同的效力。通过测试多层 I3-01v9 SAPNP 的 16 种制剂，研究了佐剂对疫苗诱导免疫的影响。使用单细胞分选，从用受体结合域 (RBD)、S2GΔHR2 刺突和 SApNP 疫苗免疫的小鼠中分离出具有不同中和广度和效力的单克隆抗体 (mAb)。在小鼠中研究了疫苗诱导免疫的机制。与可溶性尖峰相比，I3-01v9 SApNP 的保留时间长 6 倍，滤泡树突细胞树突的呈现高 4 倍，淋巴结滤泡中的生发中心反应强 5 倍。