Distinct antibody repertoires against endemic human coronaviruses in children and adults

Abstract

19Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory 20 infection in humans but immune responses to these "common cold" viruses remain 21 incompletely understood. Moreover, there is evidence emerging from independent studies 22 which suggests that endemic HCoVs can induce broadly cross-reactive T cell responses and 23 may thereby affect clinical outcomes of acute infections with the phylogenetically related 24 epidemic viruses, namely MERS-CoV and SARS-CoV-2. Here we report a comprehensive 25 retrospective analysis of CoV-specific antibody specificities in a large number of samples from 26 children and adults using Phage-Immunoprecipitation Sequencing (PhIP-Seq). We estimate 27 the seroprevalence for endemic HCoVs to range from ~4% to ~27% depending on species and 28 cohort. Most importantly, we identified a large number of novel linear B cell epitopes of HCoV 29 proteins and demonstrate that antibody repertoires against endemic HCoVs are qualitatively 30 different in children in comparison to the general adult population and healthy adult blood 31 bank donors. We show that anti-HCoV IgG specificities more frequently found among children 32 target functionally important and structurally conserved regions of the HCoV spike and 33 nucleocapsid proteins and some antibody specificities are broadly cross-reactive with 34 peptides of epidemic human and non-human coronavirus isolates. Our findings shed light on 35 the humoral immune responses to natural infection with endemic HCoVs and may have 36 important implications for understanding of the highly variable clinical outcomes of human 37 coronavirus infections, for the development of prophylactic or therapeutic monoclonal 38 antibodies and vaccine design. 39 parainfluenza viruses (HPIVs), albeit with differences in seasonality and prevalence of the 48 viruses depending on the species [5-7]. In addition to the four endemic HCoV, three epidemic 49 coronaviruses (CoVs) have emerged in humans over the last two decades, including Severe 50 Acute Respiratory Syndrome-associated CoV (SARS-CoV) [8], Middle East Respiratory 51

SARS-CoV-2 infection hospitalization, severity, criticality, and fatality rates

“…Growing evidence indicates T cell and antibody reactivity against SARS-CoV-2 in unexposed individuals [37][38][39][40], that probably reflects development of T cell and antibody immune memory to circulating 'common cold' coronaviruses, which may have in turn led to lower morbidity and mortality [37][38][39][40]. The sharedhousing dwelling structure in Qatar that contributed to the large SARS-CoV-2 epidemic [5] may have, along with the frequent international travel of Qatar's expatriate population, also contributed to higher levels of exposure to other common cold coronaviruses [41,42], thereby inducing high levels of broadly cross-reactive T cell and antibody responses. Such pre-existing immune reactivity [37][38][39][40] may have thus resulted in lower levels of SARS-CoV-2 morbidity and mortality in the population of Qatar.…”

Human leukocyte antigen class II gene diversity tunes antibody repertoires to common pathogens

“…The VirScan phage library used for PhIP-Seq in the present study comprised peptide tiles of up to 56 amino acids in length that overlap by 28 amino acids and collectively encompass the full proteomes of most known human-tropic viruses (approximately 400 species) plus many bacterial protein antigens (21). Using this technique, we identified the antibody repertoires of 798 individuals; data from two individuals were excluded from the downstream analysis as these did not meet our stringent criteria for quality control (22). We also excluded antibody specificities to species for which we found the seroprevalence in the local adult population to be below 5% (for details see the Materials and Methods section).…”

“…To account for the varying number of peptides and potential protein antigens for each microbial species encompassed by the phage display library, we adjusted the species-specific score values by normalizing the counts of significantly enriched, non-homologous peptides (i.e. pulled down peptides containing distinct linear B cell epitopes) against the total count of peptides for a given microbial species represented in the phage library, as described previously (22). We then used these adjusted species score values as a quantitative measure of the antibody repertoire breadth against each of the common microbial species identified, thereby allowing us to independently assess the effect of HLA-DRB1, -DPA1, -DPB1, -DQA1, -DQB1 zygosity.…”

“…The study cohort of adult male and female Qatari nationals and long-term residents of Qatar were randomly selected from a larger cohort of individuals taking part in a longitudinal study of the Qatar Biobank (QBB) (18) as described previously (22). Relevant demographic data of the study subjects have been described previously (22).…”

“…Elledge (Brigham and Women's Hospital and Harvard University Medical School, Boston, MA, USA). PhIP-Seq of serum samples from the 800 study subjects and peptide enrichment analysis were performed as described previously (16,17,22). In brief, we utilized an expanded version (21) of the original VirScan phage library described by Xu et.…”