Hybrid and SARS-CoV-2-vaccine immunity in kidney transplant recipients.
Anti-viral T and B cell immunity
B cell differentiation and immunity
COVID-19 vaccination
Kidney transplant recipients
T cell responses
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
01
05
2023
revised:
27
09
2023
accepted:
29
09
2023
medline:
13
11
2023
pubmed:
17
10
2023
entrez:
16
10
2023
Statut:
ppublish
Résumé
Kidney transplant recipients (KTR) are at high risk for severe COVID-19 and have demonstrated poor response to vaccination, making it unclear whether successive vaccinations offer immunity and protection. We conducted a serologically guided interventional study where KTR patients that failed to seroconvert were revaccinated and also monitored seroconversion of KTR following the Norwegian vaccination program. We analysed IgG anti-RBD Spike responses from dose 2 (n = 432) up to after the 6th (n = 37) mRNA vaccine dose. The frequency and phenotype of Spike-specific T and B cell responses were assessed in the interventional cohort after 3-4 vaccine doses (n = 30). Additionally, we evaluated the Specific T and B cell response to breakthrough infection (n = 32), measured inflammatory cytokines and broadly cross-neutralizing antibodies, and defined the incidence of COVID-19-related hospitalizations and deaths. The Norwegian KTR cohort has a male dominance (2323 males, 1297 females), PBMC were collected from 114 male and 78 female donors. After vaccine dose 3, most KTR developed Spike-specific T cell responses but had significantly reduced Spike-binding B cells and few memory cells. The B cell response included a cross-reactive subset that could bind Omicron VOC, which expanded after breakthrough infection (BTI) and gave rise to a memory IgG Boosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population. CEPI and internal funds.
Sections du résumé
BACKGROUND
BACKGROUND
Kidney transplant recipients (KTR) are at high risk for severe COVID-19 and have demonstrated poor response to vaccination, making it unclear whether successive vaccinations offer immunity and protection.
METHODS
METHODS
We conducted a serologically guided interventional study where KTR patients that failed to seroconvert were revaccinated and also monitored seroconversion of KTR following the Norwegian vaccination program. We analysed IgG anti-RBD Spike responses from dose 2 (n = 432) up to after the 6th (n = 37) mRNA vaccine dose. The frequency and phenotype of Spike-specific T and B cell responses were assessed in the interventional cohort after 3-4 vaccine doses (n = 30). Additionally, we evaluated the Specific T and B cell response to breakthrough infection (n = 32), measured inflammatory cytokines and broadly cross-neutralizing antibodies, and defined the incidence of COVID-19-related hospitalizations and deaths. The Norwegian KTR cohort has a male dominance (2323 males, 1297 females), PBMC were collected from 114 male and 78 female donors.
FINDINGS
RESULTS
After vaccine dose 3, most KTR developed Spike-specific T cell responses but had significantly reduced Spike-binding B cells and few memory cells. The B cell response included a cross-reactive subset that could bind Omicron VOC, which expanded after breakthrough infection (BTI) and gave rise to a memory IgG
INTERPRETATION
CONCLUSIONS
Boosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population.
FUNDING
BACKGROUND
CEPI and internal funds.
Identifiants
pubmed: 37844534
pii: S2352-3964(23)00399-7
doi: 10.1016/j.ebiom.2023.104833
pmc: PMC10585642
pii:
doi:
Substances chimiques
COVID-19 Vaccines
0
Immunoglobulin G
0
Antibodies, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104833Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests GG has received speaker bureaus from Pfizer, Sanofi, GSK, Vitusapotek, Bayer, and ThermoFisher; consulting fee from Norsk Pasientskadeerstatning and advisory board for Moderna, Seqirus, and Janssen. GLG has received speaker bureaus from Novartis, AbbVie, and Pfizer. KH has received speaker bureaus and travel support from Astra Zeneca. AÅ has received the support of free study drug/placebo in investigator-initiated RCT from AstraZeneca and has participated in an advisory board for AstraZeneca. LAM has received speaker bureaus from Incyte Biosciences and Janssen and a fee for expert testimony from the Norwegian Medicines Agency. HK, AA, KPL, LT, TdMK, MK, MH, AVR, JTV, FLJ, and KM declare no competing interests.