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

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



Affiliations

• PMID: 35074422
• DOI: 10.1016/j.jaci.2022.01.005

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.