Distinct antibody repertoires against endemic human coronaviruses in children and adults.

Taushif Khan,Hadi M Yassine,Guillaume Smits,Maria K Smatti,Mahbuba Rahman,Amira Saeed,Aurélie Cobat,Laurent Abel,Isabelle Migeotte,Mohammad R Hasan,Nico Marr,Zhiyong Liu,Filomeen Haerynck,Manar Ata,Qian Zhang,Isabelle Vandernoot,Isabelle Meyts,Gheyath K Nasrallah,Paul Bastard,Emmanuelle Jouanguy,Vivien Béziat ,Fatima Ali ,Jean Christophe Goffard ,Jean Laurent Casanova ,Susie S Y Huang

doi:10.1172/jci.insight.144499

Abstract

Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these “common cold” viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage immunoprecipitation sequencing. Seroprevalence of antibodies against endemic HCoVs ranged between approximately 4% and 27% depending on the species and cohort. We identified at least 136 novel linear B cell epitopes. Antibody repertoires against endemic HCoVs were qualitatively different between children and adults in that anti-HCoV IgG specificities more frequently found among children targeted functionally important and structurally conserved regions of the spike, nucleocapsid, and matrix proteins. Moreover, antibody specificities targeting the highly conserved fusion peptide region and S2′ cleavage site of the spike protein were broadly cross-reactive with peptides of epidemic human and nonhuman coronaviruses. In contrast, an acidic tandem repeat in the N-terminal region of the Nsp3 subdomain of the HCoV-HKU1 polyprotein was the predominant target of antibody responses in adult donors. Our findings shed light on the dominant species-specific and pan-CoV target sites of human antibody responses to coronavirus infection, thereby providing important insights for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.

Highlights

Four endemic human-tropic coronaviruses (HCoVs) are commonly associated with respiratory illness in humans, namely human coronaviruses (HCoVs)-229E, -NL63, -OC43, and -HKU1 [1,2,3,4]
To gain a deeper insight into human antibody responses to endemic HCoVs, we performed phage immunoprecipitation sequencing (PhIP-Seq) [29, 30] on previously collected serum or plasma samples obtained from 1431 human subjects from 3 cohorts
The VirScan phage library used for PhIP-Seq in the present study comprised peptides derived from viral proteins — each represented by peptide tiles of up to 56 amino acids in length that overlap by 28 amino acids — which collectively encompass the proteomes of a large number of viral species, including HCoV-229E, -NL63, -HKU1, and -OC43 [29, 30]

Summary

Introduction

Four endemic human-tropic coronaviruses (HCoVs) are commonly associated with respiratory illness in humans, namely HCoV-229E, -NL63, -OC43, and -HKU1 [1,2,3,4]. In addition to the 4 endemic HCoVs, 3 human-tropic epidemic coronaviruses (CoVs) have emerged over the last 2 decades, namely severe acute respiratory syndrome–CoV (SARS-CoV) [8], Middle East respiratory syndrome– CoV (MERS-CoV) [9], and SARS-CoV-2 [10], the etiological agent of coronavirus disease 2019 (COVID-19), which has reached pandemic proportions [11]. Similar to endemic HCoVs, infection of humans with epidemic CoVs is associated with a wide range of outcomes but leads more frequently to severe clinical manifestations, such as acute respiratory distress syndrome (ARDS) [12,13,14]. HCoV-229E may have been transferred from dromedary camels, similar to MERS-CoV, while HCoV-OC43 is thought to have emerged more recently from ancestors in domestic animals such as cattle or swine in the context of a pandemic at the end of the 19th century [6, 15]

Methods

Results

Conclusion