SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines.
SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines.
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DOI：
10.1126/sciimmunol.adf1421
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发表时间：
2022-12-23
影响因子：
24.8
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中科院分区：
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世界各地已开发出许多安全有效的 COVID-19 疫苗，这些疫苗利用了各种递送技术和工程策略。我们在此表明，与缺乏这些突变或自然感染的疫苗相比，含有融合前稳定 S 突变的疫苗在人体中引发抗体反应，相对于融合后 S，对 S 和 S1 亚基的识别增强。融合前S和S1抗体结合滴度与中和活性呈正相关且等价相关，并且S1定向抗体的耗尽完全消除了血浆中和活性。我们发现中和活性几乎完全针对 S1 亚基，并且变异交叉中和仅由 RBD 特异性抗体介导。我们的数据提供了一个定量框架，用于指导未来的 S 工程工作，以开发比现有技术对变体出现具有更高弹性的疫苗。 SARS-CoV-2 S1 负责所有疫苗引起的血浆中和，而交叉中和是由 RBD 特异性抗体介导的。
Numerous safe and effective COVID-19 vaccines have been developed worldwide that utilize various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S, as compared to vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by RBD-specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies. SARS-CoV-2 S1 accounts for all vaccine-elicited plasma neutralization and cross-neutralization is mediated by RBD-specific antibodies.