Longitudinal immune profiling reveals dominant epitopes mediating long-term humoral immunity in COVID-19-convalescent individuals

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

doi:10.1016/j.jaci.2022.01.005

Longitudinal immune profiling reveals dominant epitopes mediating long-term humoral immunity in COVID-19-convalescent individuals

J Allergy Clin Immunol. 2022 Apr;149(4):1225-1241. doi: 10.1016/j.jaci.2022.01.005. Epub 2022 Jan 21.

Authors

Min Li¹, Jiaojiao Liu², Renfei Lu³, Yuchao Zhang⁴, Meng Du², Man Xing², Zhenchuan Wu⁴, Xiangyin Kong⁴, Yufei Zhu⁴, Xianchao Zhou⁴, Landian Hu⁵, Chiyu Zhang⁶, Dongming Zhou⁷, Xia Jin⁸

Affiliations

¹ Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
² Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
³ Clinical Laboratory, Nantong Third Hospital Affiliated to Nantong University, Nantong, China.
⁴ CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
⁵ CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address: ldhu2013@163.com.
⁶ Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: zhangcy1999@shphc.org.cn.
⁷ Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Electronic address: zhoudongming@tmu.edu.cn.
⁸ Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: jinxia@serum-china.com.cn.

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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Viral
COVID-19*
Epitopes
Humans
Immunity, Humoral
SARS-CoV-2
Spike Glycoprotein, Coronavirus

Substances

Antibodies, Viral
Epitopes
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2