Scholarlink

<p>Receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike contains multiple classes of antibody epitopes that are associated with diverse neutralizing activities. Although both natural infection and vaccination robustly elicit RBD-reactive and neutralizing antibodies, the spike antigenic structures presented to the immune system may differ, leading to qualitative differences in the antibody responses. Using large and well-controlled cohorts, we show that the neutralizing potency index (NPI), calculated as the ratio of neutralizing titer to RBD IgG titer, is approximately fivefold lower in vaccine recipients than in convalescent individuals, independent of disease severity, comorbidities, or demographic factors. This reduction in NPI is associated with enhanced antibody targeting to non-neutralizing, yet conserved and structurally occluded RBD epitope. Molecular dynamics (MD) simulations together with the binding assay demonstrate that the occluded epitope is allosterically exposed by stabilizing mutations introduced into the vaccine spike antigen, a process mediated by a highly extended RBD-up conformation. Collectively, our findings demonstrate that RBD conformational modulation by stabilizing mutations shapes vaccine antigenicity and likely alters the epitope landscape of antibody responses.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Prefusion-stabilized SARS-CoV-2 spike reshapes antigenic hierarchy and antibody targeting against conserved and occluded epitopes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月25日

查看全文
  • Shintaro Oishi,
  • Ryutaro Kotaki,
  • Hisham M. Dokainish,
  • Saya Moriyama,
  • Shinichiro Ota,
  • Takayuki Matsumura,
  • Tomohiro Takano,
  • Taishi Onodera,
  • Yu Adachi,
  • Kazutaka Terahara,
  • Masanori Isogawa,
  • Kazuhiko Katayama,
  • Takashi Sato,
  • Masaharu Shinkai,
  • Yoshimasa Takahashi

摘要

Receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike contains multiple classes of antibody epitopes that are associated with diverse neutralizing activities. Although both natural infection and vaccination robustly elicit RBD-reactive and neutralizing antibodies, the spike antigenic structures presented to the immune system may differ, leading to qualitative differences in the antibody responses. Using large and well-controlled cohorts, we show that the neutralizing potency index (NPI), calculated as the ratio of neutralizing titer to RBD IgG titer, is approximately fivefold lower in vaccine recipients than in convalescent individuals, independent of disease severity, comorbidities, or demographic factors. This reduction in NPI is associated with enhanced antibody targeting to non-neutralizing, yet conserved and structurally occluded RBD epitope. Molecular dynamics (MD) simulations together with the binding assay demonstrate that the occluded epitope is allosterically exposed by stabilizing mutations introduced into the vaccine spike antigen, a process mediated by a highly extended RBD-up conformation. Collectively, our findings demonstrate that RBD conformational modulation by stabilizing mutations shapes vaccine antigenicity and likely alters the epitope landscape of antibody responses.