Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Sci Immunol. 2022 Dec 23;7(78):eadf1421. doi: 10.1126/sciimmunol.adf1421.
Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use 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 S subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S subunit and that variant cross-neutralization is mediated solely by receptor binding domain-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.
全球已开发出许多安全有效的 2019 年冠状病毒病疫苗，这些疫苗使用了各种传递技术和工程策略。我们在这里展示，含有融合前稳定 S 突变的疫苗在人类中引发的抗体反应增强了对 S 和 S 亚单位的识别，与缺乏这些突变或自然感染的疫苗相比。与融合后 S 相比，融合前 S 和 S 抗体结合滴度与中和活性呈正相关且等效相关，而 S 定向抗体的耗尽则完全消除了血浆中和活性。我们表明，中和活性几乎完全针对 S 亚单位，并且变体交叉中和仅由受体结合域特异性抗体介导。我们的数据为指导未来 S 工程努力提供了一个定量框架，以开发出比现有技术对变体出现更具弹性的疫苗。
