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J Allergy Clin Immunol . Longitudinal immune profiling reveals dominant epitopes mediating long-term humoral immunity in COVID-19 convalescent indi

tetano

Editor, Senior Moderator
J Allergy Clin Immunol


. 2022 Jan 21;S0091-6749(22)00073-2.
doi: 10.1016/j.jaci.2022.01.005. Online ahead of print.
Longitudinal immune profiling reveals dominant epitopes mediating long-term humoral immunity in COVID-19 convalescent individuals


Min Li[SUP] 1 [/SUP], Jiaojiao Liu[SUP] 2 [/SUP], Renfei Lu[SUP] 3 [/SUP], Yuchao Zhang[SUP] 4 [/SUP], Meng Du[SUP] 2 [/SUP], Man Xing[SUP] 2 [/SUP], Zhenchuan Wu[SUP] 4 [/SUP], Xiangyin Kong[SUP] 4 [/SUP], Yufei Zhu[SUP] 4 [/SUP], Xianchao Zhou[SUP] 4 [/SUP], Landian Hu[SUP] 4 [/SUP], Chiyu Zhang[SUP] 5 [/SUP], Dongming Zhou[SUP] 6 [/SUP], Xia Jin[SUP] 7 [/SUP]



Affiliations

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. Questions concerning serological features of long-term immunity, especially dominant epitopes mediating durable antibody responses after SARS-CoV-2 infection, still remain to be elucidated.
Objective: We aimed to dissect the kinetics and longevity of immune responses in COVID-19 patients, as well as epitopes responsible for sustained long-term humoral immunity against SARS-CoV-2.
Methods: We assessed SARS-CoV-2 immune dynamics up to 180-220 days after disease onset in 31 individuals who predominantly experienced moderate symptoms of COVID-19 and 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 individuals, 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.

Keywords: COVID-19; SARS-CoV-2; dominant epitope; humoral immunity; long-term immune response; proteome-wide peptide microarray.
 
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