Yamamoto Shinya, Yamayoshi Seiya, Ito Mutsumi, Sakai-Tagawa Yuko, Nakachi Ichiro, Baba Rie, Kamimoto Shigenobu, Ogura Takayuki, Hagiwara Shigehiro, Kato Hideaki, Nakajima Hideaki, Uwamino Yoshifumi, Yagi Kazuma, Sugaya Norio, Nagai Hiroyuki, Saito Makoto, Adachi Eisuke, Koga Michiko, Tsutsumi Takeya, Duong Calvin, Okuda Moe, Murakami Jurika, Furusawa Yuri, Ujie Michiko, Iwatsuki-Horimoto Kiyoko, Yotsuyanagi Hiroshi, Kawaoka Yoshihiro
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
iScience. 2023 Jun 25;26(7):107208. doi: 10.1016/j.isci.2023.107208. eCollection 2023 Jul 21.
SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the presence of plasma samples from convalescent patients or vaccinees to determine which amino acid substitutions affect the antigenicity of SARS-CoV-2. Several amino acid substitutions in the S2 region, as well as the N-terminal domain (NTD) and receptor-binding domain (RBD), affected the neutralization potency of plasma samples collected from vaccinees, indicating that amino acid substitutions in the S2 region as well as those in the NTD and RBD affect neutralization by vaccine-induced antibodies. Furthermore, the neutralizing potency of vaccinee plasma samples against mutant viruses we obtained or circulating viruses differed among individuals. These findings suggest that genetic backgrounds of vaccinees influence the recognition of neutralizing epitopes.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的刺突（S）蛋白已逐渐发生氨基酸替换，降低了中和抗体的效力，导致疫苗效力下降。在此，我们试图通过在康复患者或疫苗接种者的血浆样本存在的情况下传代SARS-CoV-2来获得突变病毒，以确定哪些氨基酸替换会影响SARS-CoV-2的抗原性。S2区域以及N端结构域（NTD）和受体结合结构域（RBD）中的几个氨基酸替换影响了从疫苗接种者收集的血浆样本的中和效力，表明S2区域以及NTD和RBD中的氨基酸替换会影响疫苗诱导抗体的中和作用。此外，疫苗接种者血浆样本对我们获得的突变病毒或流行病毒的中和效力在个体之间存在差异。这些发现表明，疫苗接种者的遗传背景会影响中和表位的识别。
