lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Safety and Cross-Variant Immunogenicity of a Three-Dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients

27 Pages Posted: 22 Jul 2021

See all articles by Filippo Massa

Filippo Massa

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Marion Cremoni

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Alexandre Gerard

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Hanen Grabsi

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Lory Rogier

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Mathilde Blois

Nice University Hospital - Department of Immunology

Nadia Ben Hassen

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Matthieu Rouleau

University Côte d’Azur, CNRS - Laboratory of Molecular Physio Medicine

Susana Barbosa

University Côte d’Azur, CNRS - Institute of Molecular and Cellular Pharmacology

Emanuela Martinuzzi

University Côte d’Azur, CNRS - Institute of Molecular and Cellular Pharmacology

Julien Fayada

Nice University Hospital - Laboratory of Clinical and Experimental Pathology

Ghislaine Bernard

Nice University Hospital - Department of Immunology

Guillaume Favre

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Paul Hofman

Nice University Hospital - Laboratory of Clinical and Experimental Pathology

Vincent LM Esnault

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Cecil Czerkinsky

University Côte d’Azur, CNRS - Institute of Molecular and Cellular Pharmacology

Barbara Seitz-Polski

Nice University Hospital - Department of Immunology

Nicolas Glaichenhaus

University Côte d’Azur, CNRS - Institute of Molecular and Cellular Pharmacology

Antoine Sicard

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

More...

Abstract

Background: The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. We report the first complete assessment of safety and cross-variant immunogenicity of a three-dose vaccine regimen in KT recipients.

Methods: We performed a prospective longitudinal study in sixty-one KT recipients given three doses of the BNT162b2 COVID-19 vaccine. We performed semi-structured pharmacovigilance interviews and monitored donor-specific antibodies and kidney function. We compared geometric mean titers (GMT) of anti-spike IgG, pseudo-neutralization activity against vaccine homologous and heterologous variants, frequency of spike-specific interferon (IFN)-γ-secreting cells, and antigen-induced cytokine production 28 days after the second and third doses. The immunoassays were also performed in non-transplanted individuals 28 days after the second dose to obtain reference values.

Findings: Reactions to vaccine were mild. One patient developed donor-specific anti-HLA antibodies after the second dose which could be explained by non-adherence to immunosuppressive therapy. Spike-specific IgG seroconversion raised from 44·3% (n=27) after the second dose to 62·3% (n=38) after the third dose (p<0·05). GMT increased from 528·3 (95% CI 300·0-930·1) to 2395 AU/ml (95% CI 1214-4724, p<0·0001). Serum neutralizing activity increased from 4·7% to 17·2% (Wuhan strain), 4·0% to 17·4% (alpha variant), 2·3% to 7·3% (beta variant), and 1·3% to 9·1% (gamma variant) after the third dose (p<0·0001), which remained lower than reference values. The mean frequency of IFN-γ-secreting cells increased from 19·9 (SD 56·0) to 64·0 (SD 76·8) cells/million PBMCs after the third dose (p<0·0001). A significant increase in IFN-γ responses was also observed in patients who remained seronegative after three doses (p<0·0001).

Interpretation: A third dose of the BNT162b2 vaccine increases both SARS-CoV-2-specific humoral and cellular responses in KT recipients with an acceptable tolerability profile. However, neutralizing antibody titres remain low after three doses, especially against variants of concern, and barrier measures and vaccination of the relatives remain essential.

Funding Information: This work was supported by grants from the Nice University Hospital (AOI) and the University of Cote d’Azur (IDEX).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: The study protocol complies with the principles of the Declaration of Helsinki and was approved by our institutional committee. Written informed consent was obtained from all participants and all collected data and samples were anonymized and securely stored.

Suggested Citation

Massa, Filippo and Cremoni, Marion and Gerard, Alexandre and Grabsi, Hanen and Rogier, Lory and Blois, Mathilde and Ben Hassen, Nadia and Rouleau, Matthieu and Barbosa, Susana and Martinuzzi, Emanuela and Fayada, Julien and Bernard, Ghislaine and Favre, Guillaume and Hofman, Paul and Esnault, Vincent LM and Czerkinsky, Cecil and Seitz-Polski, Barbara and Glaichenhaus, Nicolas and Sicard, Antoine, Safety and Cross-Variant Immunogenicity of a Three-Dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients. Available at SSRN: https://ssrn.com/abstract=3890865 or http://dx.doi.org/10.2139/ssrn.3890865

Filippo Massa

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Marion Cremoni

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Alexandre Gerard

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Hanen Grabsi

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Lory Rogier

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Mathilde Blois

Nice University Hospital - Department of Immunology ( email )

Nice
France

Nadia Ben Hassen

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Matthieu Rouleau

University Côte d’Azur, CNRS - Laboratory of Molecular Physio Medicine ( email )

INSERM U1065
Nice, C3M
France

Susana Barbosa

University Côte d’Azur, CNRS - Institute of Molecular and Cellular Pharmacology ( email )

INSERM U1065
Nice, C3M
France

Emanuela Martinuzzi

University Côte d’Azur, CNRS - Institute of Molecular and Cellular Pharmacology ( email )

INSERM U1065
Nice, C3M
France

Julien Fayada

Nice University Hospital - Laboratory of Clinical and Experimental Pathology ( email )

Nice
France

Ghislaine Bernard

Nice University Hospital - Department of Immunology ( email )

Nice
France

Guillaume Favre

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation

Nice
France

Paul Hofman

Nice University Hospital - Laboratory of Clinical and Experimental Pathology

France

Vincent LM Esnault

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Cecil Czerkinsky

University Côte d’Azur, CNRS - Institute of Molecular and Cellular Pharmacology ( email )

INSERM U1065
Nice, C3M
France

Barbara Seitz-Polski

Nice University Hospital - Department of Immunology

Nice, 06200
France

Nicolas Glaichenhaus

University Côte d’Azur, CNRS - Institute of Molecular and Cellular Pharmacology ( email )

INSERM U1065
Nice, C3M
France

Antoine Sicard (Contact Author)

Nice University Hospital - Department of Nephrology, Dialysis and Transplantation ( email )

Nice
France

Click here to go to TheLancet.com

Paper statistics

Abstract Views
3,682
Downloads
538
PlumX Metrics