Epitope Mapping of SARS-CoV-2 Spike Antibodies in Vaccinated Kidney Transplant Recipients Reveals Poor Spike Coverage Compared to Healthy Controls

Andrew H Karaba; William R Morgenlander; Trevor S Johnston; Camille Hage; Andrew Pekosz; Christine M Durand; Dorry L Segev; Mark A Robien; Peter S Heeger; Christian P Larsen; Joel N Blankson; William A Werbel; H Benjamin Larman; Aaron A R Tobian

doi:10.1093/infdis/jiad534

Epitope Mapping of SARS-CoV-2 Spike Antibodies in Vaccinated Kidney Transplant Recipients Reveals Poor Spike Coverage Compared to Healthy Controls

J Infect Dis. 2023 Nov 29:jiad534. doi: 10.1093/infdis/jiad534. Online ahead of print.

Authors

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA.
⁵ Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.
⁶ Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles CA, USA.
⁷ Department of Medicine, Emory University, Atlanta, Georgia, USA.
⁸ Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 38019656
DOI: 10.1093/infdis/jiad534

Abstract

Kidney transplant recipients (KTRs) develop decreased antibody titers to SARS-CoV-2 vaccination compared to healthy controls (HCs), but whether KTRs generate antibodies against key epitopes associated with neutralization is unknown. Plasma from 78 KTRs from a clinical trial of third doses of SARS-CoV-2 vaccines and 12 HCs underwent phage display immunoprecipitation and sequencing (PhIP-Seq) to map antibody responses against SARS-CoV-2. KTRs had lower antibody reactivity to SARS-CoV-2 than HCs, but KTRs and HCs recognized similar epitopes associated with neutralization. Thus, epitope gaps in antibody breadth of KTRs are unlikely responsible for decreased efficacy of SARS-CoV-2 vaccines in this immunosuppressed population.

Keywords: Antibodies; Immunocompromised Hosts; SARS-CoV-2; Transplantation; Vaccination.

Abstract

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