Graham Nancy R, Whitaker Annalis N, Strother Camilla A, Miles Ashley K, Grier Dore, McElvany Benjamin D, Bruce Emily A, Poynter Matthew E, Pierce Kristen K, Kirkpatrick Beth D, Stapleton Renee D, An Gary, Botten Jason W, Crothers Jessica W, Diehl Sean A
medRxiv. 2020 Jul 16:2020.07.15.20154443. doi: 10.1101/2020.07.15.20154443.
SARS-CoV-2 is the newly emerged virus responsible for the global COVID-19 pandemic. There is an incomplete understanding of the host humoral immune response to SARS-CoV-2 during acute infection. Host factors such as age and sex as well the kinetics and functionality of antibody responses are important factors to consider as vaccine development proceeds. The receptor-binding domain of the CoV spike (RBD-S) protein is important in host cell recognition and infection and antibodies targeting this domain are often neutralizing. In a cross-sectional study of anti-RBD-S antibodies in COVID-19 patients we found equivalent levels in male and female patients and no age-related deficiencies even out to 93 years of age. The anti-RBD-S response was evident as little as 6 days after onset of symptoms and for at least 5 weeks after symptom onset. Anti-RBD-S IgG, IgM, and IgA responses were simultaneously induced within 10 days after onset, but isotype-specific kinetics differed such that anti-RBD-S IgG was most sustained over a 5-week period. The kinetics and magnitude of neutralizing antibody formation strongly correlated with that seen for anti-RBD-S antibodies. Our results suggest age- and sex- related disparities in COVID-19 fatalities are not explained by anti-RBD-S responses. The multi-isotype anti-RBD-S response induced by live virus infection could serve as a potential marker by which to monitor vaccine-induced responses.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是引发全球新型冠状病毒肺炎(COVID-19)大流行的新出现病毒。目前对于急性感染期间宿主对SARS-CoV-2的体液免疫反应仍了解不足。随着疫苗研发的推进,年龄、性别等宿主因素以及抗体反应的动力学和功能都是需要考虑的重要因素。冠状病毒刺突蛋白的受体结合域(RBD-S)在宿主细胞识别和感染中起重要作用,靶向该结构域的抗体通常具有中和作用。在一项针对COVID-19患者抗RBD-S抗体的横断面研究中,我们发现男性和女性患者的抗体水平相当,且在93岁之前均未发现与年龄相关的抗体缺陷。抗RBD-S反应在症状出现后6天即可显现,且在症状出现后至少持续5周。症状出现后10天内同时诱导产生抗RBD-S IgG、IgM和IgA反应,但各亚型的动力学有所不同,其中抗RBD-S IgG在5周内最为持久。中和抗体形成的动力学和幅度与抗RBD-S抗体密切相关。我们的结果表明,COVID-19死亡病例中与年龄和性别相关的差异不能用抗RBD-S反应来解释。活病毒感染诱导产生的多亚型抗RBD-S反应可作为监测疫苗诱导反应的潜在标志物。