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

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.

SUBMITTER: Khan T

PROVIDER: S-EPMC7934927 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Khan Taushif T Rahman Mahbuba M Ali Fatima Al FA Huang Susie S Y SSY Ata Manar M Zhang Qian Q Bastard Paul P Liu Zhiyong Z Jouanguy Emmanuelle E Béziat Vivien V Cobat Aurélie A Nasrallah Gheyath K GK Yassine Hadi M HM Smatti Maria K MK Saeed Amira A Vandernoot Isabelle I Goffard Jean-Christophe JC Smits Guillaume G Migeotte Isabelle I Haerynck Filomeen F Meyts Isabelle I Abel Laurent L Casanova Jean-Laurent JL Hasan Mohammad R MR Marr Nico N

JCI insight 20210222 4

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 nov ...[more]

PMID: 33497357

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Project description:Community protective immunity can affect RNA virus evolution by selecting for new antigenic variants on the scale of years, exemplified by the need of annual evaluation of influenza vaccines. The extent to which this process termed antigenic drift affects coronaviruses remains unknown. Alike the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seasonal human coronaviruses (HCoV) likely emerged from animal reservoirs as new human pathogens in the past. We therefore analyzed the long-term evolutionary dynamics of the ubiquitous HCoV-229E and HCoV-OC43 in comparison with human influenza A virus (IAV) subtype H3N2. We focus on viral glycoprotein genes that mediate viral entry into cells and are major targets of host neutralizing antibody responses. Maximum likelihood and Bayesian phylogenies of publicly available gene datasets representing about three decades of HCoV and IAV evolution showed that all viruses had similar ladder-like tree shapes compatible with antigenic drift, supported by different tree shape statistics. Evolutionary rates inferred in a Bayesian framework were 6.5 × 10-4 (95% highest posterior density (HPD), 5.4-7.5 × 10-4) substitutions per site per year (s/s/y) for HCoV-229E spike (S) genes and 5.7 × 10-4 (95% HPD, 5-6.5 × 10-4) s/s/y for HCoV-OC43 S genes, which were about fourfold lower than the 2.5 × 10-3 (95% HPD, 2.3-2.7 × 10-3) s/s/y rate for IAV hemagglutinin (HA) genes. Coronavirus S genes accumulated about threefold less (P < 0.001) non-synonymous mutations (dN) over time than IAV HA genes. In both IAV and HCoV, the average rate of dN within the receptor binding domains (RBD) was about fivefold higher (P < 0.0001) than in other glycoprotein gene regions. Similarly, most sites showing evidence for positive selection occurred within the RBD (HCoV-229E, 6/14 sites, P < 0.05; HCoV-OC43, 23/38 sites, P < 0.01; IAV, 13/15 sites, P = 0.08). In sum, the evolutionary dynamics of HCoV and IAV showed several similarities, yet amino acid changes potentially representing antigenic drift occurred on a lower scale in endemic HCoV compared to IAV. It seems likely that pandemic SARS-CoV-2 evolution will bear similarities with IAV evolution including accumulation of adaptive changes in the RBD, requiring vaccines to be updated regularly, whereas higher SARS-CoV-2 evolutionary stability resembling endemic HCoV can be expected in the post-pandemic stage.

Dataset Information

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

Publications

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

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