The immune evasion of SARS-CoV-2 Omicron variants caused by multiple amino acid replacements in the receptor-binding domain (RBD) of the spike protein wanes the effectiveness of antibodies elicited by current SARS-CoV-2 booster vaccination. The vaccines that target Omicron strains have been recently developed, however, there has been a concern yet to be addressed regarding the negative aspect of the immune response known as original antigenic sin. Here, we demonstrate that the breadth of neutralizing antibodies against SARS-CoV-2 variants is barely elicited by immunizing monovalent viral antigens via vaccination or natural infection in mice and human subjects. However, vaccination of Omicron BA.1 RBD to pre-immunized mice with the original RBD conferred sustained neutralizing activity to BA.1 and BA.2 not only original pseudoviruses. The acquisition of neutralizing antibody breadth was further confirmed in vaccinated-then-Omicron convalescent human sera in which neutralizing activity against BA.1 and BA.2 pseudoviruses was highly induced. Thus, our data suggest that Omicron-specific vaccines or the infection with Omicron viruses can boost potent neutralizing antibodies to the Omicron variants even in the host pre-vaccinated with the original antigen.

中文翻译：

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使用 Omicron 刺突 RBD 进行疫苗接种可提高广泛的中和抗体水平，即使在获得对原始抗原的免疫力后也能提供持续的保护。

由刺突蛋白受体结合域 (RBD) 中的多个氨基酸置换引起的 SARS-CoV-2 Omicron 变体的免疫逃避削弱了当前 SARS-CoV-2 加强疫苗接种引发的抗体的有效性。最近开发了针对 Omicron 菌株的疫苗，但是，关于称为原始抗原原罪的免疫反应的消极方面，仍有待解决的问题。在这里，我们证明了针对 SARS-CoV-2 变体的中和抗体的广度几乎不是通过在小鼠和人类受试者中通过疫苗接种或自然感染来免疫单价病毒抗原而产生的。然而，将 Omicron BA.1 RBD 接种到用原始 RBD 预免疫的小鼠后，不仅对原始假病毒赋予了对 BA.1 和 BA.2 的持续中和活性。中和抗体广度的获得在接种后 Omicron 恢复期人血清中得到进一步证实，其中高度诱导了针对 BA.1 和 BA.2 假病毒的中和活性。因此，我们的数据表明，Omicron 特异性疫苗或 Omicron 病毒感染可以增强针对 Omicron 变体的有效中和抗体，即使在预先接种原始抗原的宿主中也是如此。