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Longitudinal immune profiling reveals dominant epitopes mediating long-term humoral immunity in COVID-19-convalescent individuals
论文作者 Li, M; Liu, JJ; Lu, RF; Zhang, YC; Du, M; Xing, M; Wu, ZC; Kong, XY; Zhu, YF; Zhou, XC; Hu, LD; Zhang, CY; Zhou, DM; Jin, X
期刊/会议名称 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
论文年度 2022
论文类别 Article
摘要 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic and contagious coronavirus that caused a global pandemic with 5.2 million fatalities to date. Questions concerning serologic features of long-term immunity, especially dominant epitopes mediating durable antibody responses after SARS-CoV-2 infection, remain to be elucidated.Objective: We aimed to dissect the kinetics and longevity of immune responses in coronavirus disease 2019 (COVID-19) patients, as well as the epitopes responsible for sustained longterm humoral immunity against SARS-CoV-2.Methods: We assessed SARS-CoV-2 immune dynamics up to 180 to 220 days after disease onset in 31 individuals who predominantly experienced moderate symptoms of COVID-19, then performed a proteome-wide profiling of dominant epitopes responsible for persistent humoral immune responses.Results: Longitudinal analysis revealed sustained SARS-CoV-2 spike protein-specific antibodies and neutralizing antibodies in COVID-19 patients, along with activation of cytokine production at early stages after SARS-CoV-2 infection. Highly reactive epitopes that were capable of mediating long-term antibody responses were shown to be located at the spike and ORF1ab proteins. Key epitopes of the SARS-CoV-2 spike protein were mapped to the N-terminal domain of the S1 subunit and the S2 subunit, with varying degrees of sequence homology among endemic human coronaviruses and high sequence identity between the early SARS-CoV-2 (Wuhan-Hu 1) and current circulating variants.Conclusion: SARS-CoV-2 infection induces persistent humoral immunity in COVID-19-convalescent individuals by targeting dominant epitopes located at the spike and ORF1ab proteins that mediate long-term immune responses. Our findings provide a path to aid rational vaccine design and diagnostic development. (J Allergy Clin Immunol 2022;149:1225-41.)
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