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. 2024 May 15;229(5):1366-1371.
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

Andrew H Karaba  1 , William R Morgenlander  2 , Trevor S Johnston  1 , Camille Hage  1 , Andrew Pekosz  1   3 , Christine M Durand  1 , Dorry L Segev  4 , Mark A Robien  5 , Peter S Heeger  6 , Christian P Larsen  7 , Joel N Blankson  1 , William A Werbel  1 , H Benjamin Larman  2 , Aaron A R Tobian  8
Affiliations

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

Andrew H Karaba et al. J Infect Dis. .

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.

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Conflict of interest statement

Potential conflicts of interest. D. L. S. reports receiving consulting and/or speaking honoraria from AstraZeneca, CareDx, Moderna Therapeutics, Novavax, Regeneron, Springer Publishing, Houston Methodist, Northwell Health, Optum Health Education, Sanofi, and WebMd. W. A. W. has received consulting and/or speaking fees from AstraZeneca, GlobalData, China Medical Tribune, Medical Learning Institute (CME), and advisory board fees from Novavax. A. H. K. has received consulting fees from Roche Diagnostics and Hologic, Inc; and speaking fees from PRIME Education (CME). H. B. L. is an inventor on an issued patent (US20160320406A) filed by Brigham and Women's Hospital that covers the use of PhIP-Seq for antiviral antibody detection; and is a founder of ImmuneID, Portal Bioscience, Alchemab, and Infinity Bio. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
A, Heatmap of SARS-CoV-2 spike epitope reactivities for KTRs and HCs before (Pre) and 30 days after (Post) receiving a third dose of a SARS-CoV-2 mRNA vaccine. B, Number of unique spike epitope reactivities in each group. Groups were compared by Wilcoxon test. C, Net spike reactivity in each group. Groups were compared by Wilcoxon test. D, Differential reactivity to each spike epitope between HCs and KTRs after the third vaccine dose. The P value for each peptide was determined with a Fisher exact test. ***P < .001. Abbreviations: CS, cleavage site; FP, fusion peptide; HC, healthy control; HR, heptad repeat; KTR, kidney transplant recipient; log2(fc), fold change; NS, not significant; NTD, N terminal domain; RBD, receptor-binding domain; S, spike; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SD, subdomain.
Figure 2.
Figure 2.
A, Viral scores for ccCoVs prior to receiving a third vaccine dose compared to total SARS-CoV-2 spike IgG after receiving a third vaccine dose for both healthy controls and KTRs. B, Viral scores of SARS-CoV-2 and total SARS-CoV-2 spike IgG were compared at the same postboost time point. C, Negative log10  P value from Pearson correlations between CoV spike epitope reactivities and NT-AUC in kidney transplant recipients. Peptides from the 4 common cold coronaviruses and SARS-CoV-2 were mapped to the SARS-CoV-2 protein. D, Pearson correlation coefficients for spike peptides that significantly correlated with NT-AUC. ***P < .001. Abbreviations: BAU, binding antibody unit; ccCoV, common cold coronavirus; CS, cleavage site; FP, fusion peptide; HR, heptad repeat; IgG, immunoglobulin G; KTR, kidney transplant recipients; NT-AUC, neutralizing titer area under the curve; NTD, N terminal domain; PhIP, phage display immunoprecipitation; RBD, receptor-binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
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References

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