tetano
Editor, Senior Moderator
JCI Insight
. 2021 Jan 26;144499.
doi: 10.1172/jci.insight.144499. Online ahead of print.
Distinct antibody repertoires against endemic human coronaviruses in children and adults
Taushif Khan[SUP] 1 [/SUP], Mahbuba Rahman[SUP] 1 [/SUP], Fatima Al Ali[SUP] 2 [/SUP], Susie Sy Huang[SUP] 1 [/SUP], Manar Ata[SUP] 1 [/SUP], Qian Zhang[SUP] 3 [/SUP], Paul Bastard[SUP] 4 [/SUP], Zhiyong Liu[SUP] 3 [/SUP], Emmanuelle Jouanguy[SUP] 4 [/SUP], Vivien Beziat[SUP] 5 [/SUP], Aur?lie Cobat[SUP] 4 [/SUP], Gheyath K Nasrallah[SUP] 6 [/SUP], Hadi M Yassine[SUP] 6 [/SUP], Maria K Smatti[SUP] 7 [/SUP], Amira Saeed[SUP] 8 [/SUP], Isabelle Vandernoot[SUP] 9 [/SUP], Jean-Christophe Goffard[SUP] 10 [/SUP], Guillaume Smits[SUP] 9 [/SUP], Isabelle Migeotte[SUP] 11 [/SUP], Filomeen Haerynck[SUP] 12 [/SUP], Isabelle Meyts[SUP] 13 [/SUP], Laurent Abel[SUP] 14 [/SUP], Jean-Laurent Casanova[SUP] 15 [/SUP], Mohammad R Hasan[SUP] 8 [/SUP], Nico Marr[SUP] 2 [/SUP]
Affiliations
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 to endemic HCoVs ranged between ~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 non-human 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.
Keywords: Immunoglobulins; Immunology; Infectious disease.
. 2021 Jan 26;144499.
doi: 10.1172/jci.insight.144499. Online ahead of print.
Distinct antibody repertoires against endemic human coronaviruses in children and adults
Taushif Khan[SUP] 1 [/SUP], Mahbuba Rahman[SUP] 1 [/SUP], Fatima Al Ali[SUP] 2 [/SUP], Susie Sy Huang[SUP] 1 [/SUP], Manar Ata[SUP] 1 [/SUP], Qian Zhang[SUP] 3 [/SUP], Paul Bastard[SUP] 4 [/SUP], Zhiyong Liu[SUP] 3 [/SUP], Emmanuelle Jouanguy[SUP] 4 [/SUP], Vivien Beziat[SUP] 5 [/SUP], Aur?lie Cobat[SUP] 4 [/SUP], Gheyath K Nasrallah[SUP] 6 [/SUP], Hadi M Yassine[SUP] 6 [/SUP], Maria K Smatti[SUP] 7 [/SUP], Amira Saeed[SUP] 8 [/SUP], Isabelle Vandernoot[SUP] 9 [/SUP], Jean-Christophe Goffard[SUP] 10 [/SUP], Guillaume Smits[SUP] 9 [/SUP], Isabelle Migeotte[SUP] 11 [/SUP], Filomeen Haerynck[SUP] 12 [/SUP], Isabelle Meyts[SUP] 13 [/SUP], Laurent Abel[SUP] 14 [/SUP], Jean-Laurent Casanova[SUP] 15 [/SUP], Mohammad R Hasan[SUP] 8 [/SUP], Nico Marr[SUP] 2 [/SUP]
Affiliations
- PMID: 33497357
- 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 to endemic HCoVs ranged between ~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 non-human 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.
Keywords: Immunoglobulins; Immunology; Infectious disease.