Hybrid and SARS-CoV-2-vaccine immunity in kidney transplant recipientsResearch in context
Hassen Kared,
Amin Alirezaylavasani,
Katrine Persgård Lund,
Adity Chopra,
Lisa Tietze,
Taissa de Matos Kasahara,
Guro Løvik Goll,
Gunnveig Grødeland,
Mari Kaarbø,
Anna Varberg Reisæter,
Markus Hovd,
Kristian Heldal,
John Torgils Vaage,
Fridtjof Lund-Johansen,
Karsten Midtvedt,
Anders Åsberg,
Ludvig A. Munthe
Affiliations
Hassen Kared
KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway; Corresponding author.
Amin Alirezaylavasani
KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway
Katrine Persgård Lund
KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway
Adity Chopra
Department of Immunology, Oslo University Hospital, Oslo, Norway; ImmunoLingo Convergence Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Lisa Tietze
Department of Immunology, Oslo University Hospital, Oslo, Norway; ImmunoLingo Convergence Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Taissa de Matos Kasahara
Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Guro Løvik Goll
Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway
Gunnveig Grødeland
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway
Mari Kaarbø
Department of Microbiology, Oslo University Hospital, Oslo, Norway
Anna Varberg Reisæter
Department of Transplantation Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway
Markus Hovd
Department of Transplantation Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway; Department of Pharmacy, University of Oslo, Oslo, Norway
Kristian Heldal
Department of Transplantation Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway
John Torgils Vaage
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway
Fridtjof Lund-Johansen
Department of Immunology, Oslo University Hospital, Oslo, Norway; ImmunoLingo Convergence Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Karsten Midtvedt
Department of Transplantation Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway
Anders Åsberg
Department of Transplantation Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway; Norwegian Renal Registry, Oslo University Hospital-Rikshospitalet, Oslo, Norway; Department of Pharmacy, University of Oslo, Oslo, Norway
Ludvig A. Munthe
KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway; Corresponding author.
Summary: 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: 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: 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+ B cell response. After BTI, KTR had increased Spike-specific T cells, emergent non-Spike T and B cell responses, and a systemic inflammatory signature. Late seroconversion occurred after doses 5–6, but 38% (14/37) of KTR had no detectable immunity even after multiple vaccine doses. Interpretation: Boosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population. Funding: CEPI and internal funds.
