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. 2024 May 15;229(5):1366-1371. doi: 10.1093/infdis/jiad534.

Authors

Affiliations

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

Abstract

Kidney transplant recipients (KTRs) develop decreased antibody titers to severe acute respiratory syndrome coronavirus 2 (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. Clinical Trials Registration. NCT04969263.

Keywords: SARS-CoV-2; antibodies; immunocompromised hosts; transplantation; vaccination.

MeSH terms

Adult
Aged
Antibodies, Neutralizing / blood
Antibodies, Neutralizing / immunology
Antibodies, Viral* / blood
Antibodies, Viral* / immunology
COVID-19 Vaccines* / administration & dosage
COVID-19 Vaccines* / immunology
COVID-19* / immunology
COVID-19* / prevention & control
Case-Control Studies
Epitope Mapping*
Epitopes / immunology
Female
Humans
Kidney Transplantation*
Male
Middle Aged
SARS-CoV-2* / immunology
Spike Glycoprotein, Coronavirus* / immunology
Transplant Recipients*
Vaccination

Associated data

ClinicalTrials.gov/NCT04969263

Abstract

MeSH terms

Associated data

Grants and funding