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10.1371/journal.pone.0256482

http://scihub22266oqcxt.onion/10.1371/journal.pone.0256482
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34449792!8396729!34449792
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suck abstract from ncbi


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pmid34449792      PLoS+One 2021 ; 16 (8): e0256482
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  • Original antigenic sin responses to Betacoronavirus spike proteins are observed in a mouse model, but are not apparent in children following SARS-CoV-2 infection #MMPMID34449792
  • Lapp SA; Edara VV; Lu A; Lai L; Hussaini L; Chahroudi A; Anderson LJ; Suthar MS; Anderson EJ; Rostad CA
  • PLoS One 2021[]; 16 (8): e0256482 PMID34449792show ga
  • BACKGROUND: The effects of pre-existing endemic human coronavirus (HCoV) immunity on SARS-CoV-2 serologic and clinical responses are incompletely understood. OBJECTIVES: We sought to determine the effects of prior exposure to HCoV Betacoronavirus HKU1 spike protein on serologic responses to SARS-CoV-2 spike protein after intramuscular administration in mice. We also sought to understand the baseline seroprevalence of HKU1 spike antibodies in healthy children and to measure their correlation with SARS-CoV-2 binding and neutralizing antibodies in children hospitalized with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C). METHODS: Groups of 5 mice were injected intramuscularly with two doses of alum-adjuvanted HKU1 spike followed by SARS-CoV-2 spike; or the reciprocal regimen of SARS-Cov-2 spike followed by HKU1 spike. Sera collected 21 days following each injection was analyzed for IgG antibodies to HKU1 spike, SARS-CoV-2 spike, and SARS-CoV-2 neutralization. Sera from children hospitalized with acute COVID-19, MIS-C or healthy controls (n = 14 per group) were analyzed for these same antibodies. RESULTS: Mice primed with SARS-CoV-2 spike and boosted with HKU1 spike developed high titers of SARS-CoV-2 binding and neutralizing antibodies; however, mice primed with HKU1 spike and boosted with SARS-CoV-2 spike were unable to mount neutralizing antibodies to SARS-CoV-2. HKU1 spike antibodies were detected in all children with acute COVID-19, MIS-C, and healthy controls. Although children with MIS-C had significantly higher HKU1 spike titers than healthy children (GMT 37239 vs. 7551, P = 0.012), these titers correlated positively with both SARS-CoV-2 binding (r = 0.7577, P<0.001) and neutralizing (r = 0.6201, P = 0.001) antibodies. CONCLUSIONS: Prior murine exposure to HKU1 spike protein completely impeded the development of neutralizing antibodies to SARS-CoV-2, consistent with original antigenic sin. In contrast, the presence of HKU1 spike IgG antibodies in children with acute COVID-19 or MIS-C was not associated with diminished neutralizing antibody responses to SARS-CoV-2.
  • |Adolescent[MESH]
  • |Animals[MESH]
  • |Antibodies, Neutralizing/*immunology[MESH]
  • |Antibodies, Viral/immunology[MESH]
  • |Antigen-Antibody Reactions[MESH]
  • |Betacoronavirus/*metabolism[MESH]
  • |COVID-19/immunology/pathology/virology[MESH]
  • |Child[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Immunoglobulin G/blood/immunology[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Mice, Inbred BALB C[MESH]
  • |SARS-CoV-2/isolation & purification/metabolism[MESH]


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