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Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality.
Morgenlander, William R; Henson, Stephanie N; Monaco, Daniel R; Chen, Athena; Littlefield, Kirsten; Bloch, Evan M; Fujimura, Eric; Ruczinski, Ingo; Crowley, Andrew R; Natarajan, Harini; Butler, Savannah E; Weiner, Joshua A; Li, Mamie Z; Bonny, Tania S; Benner, Sarah E; Balagopal, Ashwin; Sullivan, David; Shoham, Shmuel; Quinn, Thomas C; Eshleman, Susan H; Casadevall, Arturo; Redd, Andrew D; Laeyendecker, Oliver; Ackerman, Margaret E; Pekosz, Andrew; Elledge, Stephen J; Robinson, Matthew; Tobian, Aaron Ar; Larman, H Benjamin.
  • Morgenlander WR; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Henson SN; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Monaco DR; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Chen A; Department of Biostatistics, and.
  • Littlefield K; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Bloch EM; Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Fujimura E; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, and Department of Genetics, Program in Virology, Harvard Medical School, Boston, Massachusetts, USA.
  • Ruczinski I; Department of Biostatistics, and.
  • Crowley AR; Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA.
  • Natarajan H; Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA.
  • Butler SE; Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA.
  • Weiner JA; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
  • Li MZ; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, and Department of Genetics, Program in Virology, Harvard Medical School, Boston, Massachusetts, USA.
  • Bonny TS; Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Benner SE; Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Balagopal A; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Sullivan D; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Shoham S; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Quinn TC; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Eshleman SH; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Casadevall A; Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
  • Redd AD; Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Laeyendecker O; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Ackerman ME; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Pekosz A; Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
  • Elledge SJ; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Robinson M; Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
  • Tobian AA; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
  • Larman HB; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
J Clin Invest ; 131(7)2021 04 01.
Article in English | MEDLINE | ID: covidwho-1166661
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ABSTRACT
SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Randomized controlled trials Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: JCI146927

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Randomized controlled trials Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: JCI146927