Immunogenicity of a 3rd Dose of Mrna Covid-19 Vaccine in Kidney Transplant Recipients Who Failed to Respond to 2 Prior Doses

W. Werbel¹, A. Karaba¹, T. Chiang¹, T. Liang¹, A. Massie¹, M. Bettinotti¹, W. Clarke¹, N. Watson², A. Tobian¹, C. Durand¹, N. Bridges², D. Rostrosen², C. Larsen³, P. Heeger⁴, D. Segev¹

¹Johns Hopkins, Baltimore, MD, ²NIAID, Bethesda, MD, ³Emory University, Atlanta, GA, ⁴Mt. Sinai School of Medicine, New York, NY

Meeting: 2022 American Transplant Congress

Abstract number: 687

Keywords: Antibodies, COVID-19, Kidney transplantation, Vaccination

Topic: Clinical Science » Infection Disease » 24 - All Infections (Excluding Kidney & Viral Hepatitis)

Session Information

Session Name: All Infections (Excluding Kidney & Viral Hepatitis) I

Session Type: Poster Abstract

Date: Saturday, June 4, 2022

Session Time: 5:30pm-7:00pm

Presentation Time: 5:30pm-7:00pm

Location: Hynes Halls C & D

*Purpose: Kidney transplant recipients (KTRs) have diminished immune response and protection after 2-dose mRNA COVID-19 vaccination. It is unknown if additional doses improve neutralization of variants of concern (VOC) in KTRs with prior poor seroresponse.

*Methods: Adult KTRs with negative (<0.8 U/mL) or low (≤50 U/ml) anti-RBD Ig (Roche Elecsys anti-SARS-CoV-2-S) after 2-dose mRNA series were given a homologous 3^rd dose (D3). Anti-RBD and VOC surrogate neutralization (%ACE2i) were measured 30 days post D3; responses were stratified by baseline anti-RBD. Reactogenicity, serial SARS-CoV-2 swabs, and donor-specific antibody (DSA) were assessed.

*Results: 81 KTRs (50% negative anti-RBD) received D3 (72% BNT162b2, 28% mRNA-1273) at median 167 days post D2 (Table). Median (IQR) anti-RBD increase was 410 (8-2309) U/mL with 69% (40% negative vs 98% low anti-RBD) achieving day 30 anti-RBD >50 U/ml (Fig1a). 22% remained seronegative. Non-response was associated with lower baseline lymphocyte count (median 770 vs 1160 cells/uL; p=0.05) and IgG (median 779 vs 979 mg/dL; p<0.01), but not demographics, vaccine, or immunosuppressives. Median (IQR) delta variant %ACE2i increased from 6% (3-7) to 10% (4-22) (p<0.001), a 1% (0-5) increase in negative vs 13% (5-25) in low anti-RBD. %ACE2i was linearly associated with anti-RBD ≥100 U/mL (all VOC shown in Fig1b); 64% of KTRs with anti-RBD ≥250 U/mL had delta %ACE2i >20. There were 3 cases of mild-moderate COVID-19 ≥7 days post-D3, with pre-infection anti-RBD <0.4, 22, 76 U/mL and delta %ACE2i 6, 9, and 16, respectively. There was no acute rejection, nor increased or de novo DSA.

*Conclusions: A 3^rd mRNA vaccine dose increased anti-RBD and VOC neutralization in KTRs without inducing clinical alloimmunity, yet 45% with negative baseline anti-RBD remained seronegative without delta variant neutralization. Trials are ongoing to test immune response augmentation in this subgroup via temporary immunosuppression reduction or heterologous boosting.

To cite this abstract in AMA style:

Werbel W, Karaba A, Chiang T, Liang T, Massie A, Bettinotti M, Clarke W, Watson N, Tobian A, Durand C, Bridges N, Rostrosen D, Larsen C, Heeger P, Segev D. Immunogenicity of a 3rd Dose of Mrna Covid-19 Vaccine in Kidney Transplant Recipients Who Failed to Respond to 2 Prior Doses [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/immunogenicity-of-a-3rd-dose-of-mrna-covid-19-vaccine-in-kidney-transplant-recipients-who-failed-to-respond-to-2-prior-doses/. Accessed May 18, 2025.

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