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Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2.
Natarajan, Harini; Xu, Shiwei; Crowley, Andrew R; Butler, Savannah E; Weiner, Joshua A; Bloch, Evan M; Littlefield, Kirsten; Benner, Sarah E; Shrestha, Ruchee; Ajayi, Olivia; Wieland-Alter, Wendy; Sullivan, David; Shoham, Shmuel; Quinn, Thomas C; Casadevall, Arturo; Pekosz, Andrew; Redd, Andrew D; Tobian, Aaron A R; Connor, Ruth I; Wright, Peter F; Ackerman, Margaret E.
  • Natarajan H; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, USA.
  • Xu S; Program in Quantitative Biological Sciences, Dartmouth College, Hanover, NH, USA.
  • Crowley AR; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, USA.
  • Butler SE; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, USA.
  • Weiner JA; Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH, 03755, USA.
  • Bloch EM; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Littlefield K; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Benner SE; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Shrestha R; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Ajayi O; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Wieland-Alter W; Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
  • Sullivan D; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Shoham S; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Quinn TC; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Casadevall A; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Pekosz A; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Redd AD; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Tobian AAR; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Connor RI; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Wright PF; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Ackerman ME; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
BMC Immunol ; 23(1): 7, 2022 02 16.
Article in English | MEDLINE | ID: covidwho-1745516
ABSTRACT

BACKGROUND:

While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined.

METHODS:

We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action.

RESULTS:

To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion.

CONCLUSIONS:

Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Long Covid / Vaccines Language: English Journal: BMC Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S12865-022-00480-w

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Long Covid / Vaccines Language: English Journal: BMC Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S12865-022-00480-w