Longitudinal immune profiling reveals dominant epitopes mediating long-term humoral immunity in COVID-19–convalescent individuals
Autor: | Min Li, Jiaojiao Liu, Renfei Lu, Yuchao Zhang, Meng Du, Man Xing, Zhenchuan Wu, Xiangyin Kong, Yufei Zhu, Xianchao Zhou, Landian Hu, Chiyu Zhang, Dongming Zhou, Xia Jin |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
nsp
Nonstructural protein SARS Severe acute respiratory syndrome viruses Immunology RBD Receptor binding domain PBS-T PBS–Tween 20 Antibodies Viral Article Epitopes dominant epitope BSA Bovine serum albumin humoral immunity S Spike protein Immunology and Allergy CoV Coronavirus Humans NTD N-terminal domain long-term immune response COVID-19 Coronavirus disease 2019 NT50 50% neutralization titer SARS-CoV-2 MERS Middle East respiratory syndrome virus diseases COVID-19 biochemical phenomena metabolism and nutrition M Membrane protein PBS Phosphate-buffered saline PDB Protein Data Bank (http://www.wwpdb.org/) Immunity Humoral N Nucleocapsid protein FP Fusion peptide Spike Glycoprotein Coronavirus ORF Open reading frame proteome-wide peptide microarray OD Optical density |
Zdroj: | The Journal of Allergy and Clinical Immunology |
ISSN: | 1097-6825 0091-6749 |
Popis: | 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 long-term 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. |
Databáze: | OpenAIRE |
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