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

Author:

Karaba Andrew H1,Morgenlander William R2,Johnston Trevor S1,Hage Camille1,Pekosz Andrew13ORCID,Durand Christine M1,Segev Dorry L4,Robien Mark A5,Heeger Peter S6,Larsen Christian P7,Blankson Joel N1,Werbel William A1,Larman H Benjamin2,Tobian Aaron A R8ORCID

Affiliation:

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, New York 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

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.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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