Department of Data Science, University of California San Diego, La Jolla, CA 92093, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Viruses. 2021 Mar 20;13(3):516. doi: 10.3390/v13030516.
While SARS-CoV-2 specific neutralizing antibodies have been developed for therapeutic purposes, the specific viral triggers that drive the generation of SARS-CoV-2 specific IgG and IgM antibodies remain only partially characterized. Moreover, it is unknown whether endogenously derived antibodies drive viral clearance that might result in mitigation of clinical severity during natural infection. We developed a series of non-linear mathematical models to investigate whether SARS-CoV-2 viral and antibody kinetics are coupled or governed by separate processes. Patients with severe disease had a higher production rate of IgG but not IgM antibodies. Maximal levels of both isotypes were governed by their production rate rather than different saturation levels between people. Our results suggest that an exponential surge in IgG levels occurs approximately 5-10 days after symptom onset with no requirement for continual antigenic stimulation. SARS-CoV-2 specific IgG antibodies appear to have limited to no effect on viral dynamics but may enhance viral clearance late during primary infection resulting from the binding effect of antibody to virus, rather than neutralization. In conclusion, SARS-CoV-2 specific IgG antibodies may play only a limited role in clearing infection from the nasal passages despite providing long-term immunity against infection following vaccination or prior infection.
虽然已经开发出针对 SARS-CoV-2 的特异性中和抗体用于治疗目的,但驱动 SARS-CoV-2 特异性 IgG 和 IgM 抗体产生的特定病毒触发因素仅部分得到了描述。此外,尚不清楚内源性抗体是否会促进病毒清除,从而减轻自然感染期间的临床严重程度。我们开发了一系列非线性数学模型来研究 SARS-CoV-2 病毒和抗体动力学是否相互关联或受单独过程控制。重症患者 IgG 抗体的产生速率较高,但 IgM 抗体则不然。两种同型的最高水平都由其产生速率决定,而不是人与人之间的不同饱和度水平决定。我们的研究结果表明,IgG 水平大约在症状出现后 5-10 天呈指数增长,无需持续的抗原刺激。SARS-CoV-2 特异性 IgG 抗体对病毒动力学似乎没有影响,但可能会增强初次感染后期的病毒清除,这是由于抗体与病毒结合的效应,而不是中和作用。总之,尽管接种疫苗或先前感染后可提供针对感染的长期免疫力,但 SARS-CoV-2 特异性 IgG 抗体可能仅在清除鼻腔感染方面发挥有限作用。