Crowley Andrew R, Natarajan Harini, Hederman Andrew P, Bobak Carly A, Weiner Joshua A, Wieland-Alter Wendy, Lee Jiwon, Bloch Evan M, Tobian Aaron A R, Redd Andrew D, Blankson Joel N, Wolf Dana, Goetghebuer Tessa, Marchant Arnaud, Connor Ruth I, Wright Peter F, Ackerman Margaret E
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, USA.
Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
medRxiv. 2021 Oct 28:2021.10.27.21265574. doi: 10.1101/2021.10.27.21265574.
Pre-existing antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the β-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity.
对地方性冠状病毒（CoV）存在的交叉反应性抗体可能会对COVID-19疫苗接种和感染的抗体反应产生或好或坏的影响。在这项针对急性感染、康复和接种疫苗受试者的黏膜和全身体液免疫的观察性研究中，我们以亚结构域分辨率测试了针对地方性CoV刺突（S）蛋白的交叉反应性。在所有测试的自然感染队列中均观察到反应增强，尤其是对β-CoV OC43的反应增强，并且与对SARS-CoV-2的反应相关。这种反应的动力学和所涉及的免疫球蛋白类型表明，感染会增强先前因接触地方性CoV而产生的交叉反应性抗体谱系。虽然需要进一步研究以确定这种回忆反应是有益还是有害，但增强的抗体主要靶向病毒刺突中保守性更好的S2亚结构域，并且与中和活性无关。相比之下，使用稳定化刺突mRNA疫苗进行接种并没有显著增强交叉反应性抗体，这表明其抗原性和免疫原性有所不同。总之，本研究提供的证据表明，针对地方性CoV的抗体在SARS-CoV-2感染后会得到显著增强，但在接种稳定化S疫苗后则不会，并且根据构象或其他因素，刺突蛋白的S2亚结构域会引发快速回忆的、以IgG为主的缺乏中和活性的反应。
