Persistent SARS-CoV-2–specific immune defects in kidney transplant recipients following third mRNA vaccine dose

CPAT investigators

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Kidney transplant recipients (KTRs) show poorer response to SARS-CoV-2 mRNA vaccination, yet response patterns and mechanistic drivers following third doses are ill-defined. We administered third monovalent mRNA vaccines to n = 81 KTRs with negative or low-titer anti-receptor binding domain (RBD) antibody (n = 39 anti-RBDNEG; n = 42 anti-RBDLO), compared with healthy controls (HCs, n = 19), measuring anti-RBD, Omicron neutralization, spike-specific CD8+%, and SARS-CoV-2–reactive T cell receptor (TCR) repertoires. By day 30, 44% anti-RBDNEG remained seronegative; 5% KTRs developed BA.5 neutralization (vs 68% HCs, P <.001). Day 30 spike-specific CD8+% was negative in 91% KTRs (vs 20% HCs; P =.07), without correlation to anti-RBD (rs = 0.17). Day 30 SARS-CoV-2–reactive TCR repertoires were detected in 52% KTRs vs 74% HCs (P =.11). Spike-specific CD4+ TCR expansion was similar between KTRs and HCs, yet KTR CD8+ TCR depth was 7.6-fold lower (P =.001). Global negative response was seen in 7% KTRs, associated with high-dose MMF (P =.037); 44% showed global positive response. Of the KTRs, 16% experienced breakthrough infections, with 2 hospitalizations; prebreakthrough variant neutralization was poor. Absent neutralizing and CD8+ responses in KTRs indicate vulnerability to COVID-19 despite 3-dose mRNA vaccination. Lack of neutralization despite CD4+ expansion suggests B cell dysfunction and/or ineffective T cell help. Development of more effective KTR vaccine strategies is critical.

Original languageEnglish
Pages (from-to)744-758
Number of pages15
JournalAmerican Journal of Transplantation
Volume23
Issue number6
DOIs
StatePublished - Jun 2023

Keywords

  • SARS-CoV-2
  • antibody
  • clinical trial
  • immunogenicity
  • kidney transplant
  • vaccination

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