1. Longitudinal immune profiling reveals dominant epitopes mediating long-term humoral immunity in COVID-19–convalescent individuals
- Author
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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, and Xia Jin
- Subjects
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 - Abstract
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.
- Published
- 2022