Vaccination with the Omicron spike RBD boosts broadly neutralizing antibody levels and confers sustained protection even after acquiring immunity to the original antigen
Vaccination with the Omicron spike RBD boosts broadly neutralizing antibody levels and confers sustained protection even after acquiring immunity to the original antigen
复制标题
DOI：
10.1093/intimm/dxac055
复制
发表时间：
2023-01-12
影响因子：
4.4
通讯作者：
Yasuda, Tomoharu
中科院分区：
文献类型：
--
作者：
Azuma, Hitoshi;Kawano, Yohei;Yasuda, Tomoharu
刺突蛋白受体结合域（RBD）的多个氨基酸替换导致SARS-CoV-2 Omicron变异的免疫逃避，降低了当前SARS-CoV-2加强疫苗接种引发的抗体的有效性。针对欧米克隆菌株的疫苗最近已经开发出来，但是，关于被称为原始抗原原的免疫反应的负面方面，还存在一个有待解决的问题。在这里，我们证明了在小鼠和人类受试者中，通过疫苗接种或自然感染免疫单价病毒抗原几乎不能激发针对SARS-CoV-2变体的中和抗体的广度。然而，用原RBD预先免疫的小鼠接种Omicron BA.1 RBD，不仅对原假病毒BA.1和BA.2具有持续的中和活性。中和抗体宽度的获得在接种后的omicron恢复期人血清中得到进一步证实，其中对BA.1和BA.2假病毒的中和活性被高度诱导。因此，我们的数据表明，即使在预先接种了原始抗原的宿主中，Omicron特异性疫苗或感染Omicron病毒也可以增强针对Omicron变体的有效中和抗体。
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.