Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients
Background: The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. Here, we provide a thorough assessment of the immunogenicity of a three-dose COVID-19 vaccine regimen in this population. Methods: We performed a prospective longitudinal study in...
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2021
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oai:doaj.org-article:6aec33f0dd6e4ddba8069d07e0e047f12021-11-10T04:28:13ZSafety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients2352-396410.1016/j.ebiom.2021.103679https://doaj.org/article/6aec33f0dd6e4ddba8069d07e0e047f12021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352396421004734https://doaj.org/toc/2352-3964Background: The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. Here, we provide a thorough assessment of the immunogenicity of a three-dose COVID-19 vaccine regimen in this population. 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 levels 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. 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). The mean level of spike-specific IgG increased from 1620 (SD, 3460) to 8772 (SD, 16733) AU/ml (p<0·0001). Serum neutralizing activity increased after the third dose for all variants of concern tested including the Delta variant (p<0·0001). The frequency of spike-specific 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 cross-variant neutralizing antibody and cellular responses in KT recipients with an acceptable tolerability profile. Funding: Nice University Hospital, University Cote d'Azur.Filippo Massa, PhDMarion Cremoni, MDAlexandre Gérard, MDHanen GrabsiLory RogierMathilde Blois, MDChloé Couzin, MDNadia Ben HassenMatthieu Rouleau, PhDSusana Barbosa, PhDEmanuela Martinuzzi, PhDJulien FayadaGhislaine Bernard, MD-PhDGuillaume Favre, MD-PhDPaul Hofman, MD-PhDVincent L.M. Esnault, MD-PhDCecil Czerkinsky, MD-PhDBarbara Seitz-Polski, MD-PhDNicolas Glaichenhaus, PhDAntoine Sicard, MD-PhDElsevierarticleCOVID-19mRNA vaccinevariants of concern, kidney transplantationImmunogenicityMedicineRMedicine (General)R5-920ENEBioMedicine, Vol 73, Iss , Pp 103679- (2021) |
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COVID-19 mRNA vaccine variants of concern, kidney transplantation Immunogenicity Medicine R Medicine (General) R5-920 |
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COVID-19 mRNA vaccine variants of concern, kidney transplantation Immunogenicity Medicine R Medicine (General) R5-920 Filippo Massa, PhD Marion Cremoni, MD Alexandre Gérard, MD Hanen Grabsi Lory Rogier Mathilde Blois, MD Chloé Couzin, MD Nadia Ben Hassen Matthieu Rouleau, PhD Susana Barbosa, PhD Emanuela Martinuzzi, PhD Julien Fayada Ghislaine Bernard, MD-PhD Guillaume Favre, MD-PhD Paul Hofman, MD-PhD Vincent L.M. Esnault, MD-PhD Cecil Czerkinsky, MD-PhD Barbara Seitz-Polski, MD-PhD Nicolas Glaichenhaus, PhD Antoine Sicard, MD-PhD Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients |
| description |
Background: The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. Here, we provide a thorough assessment of the immunogenicity of a three-dose COVID-19 vaccine regimen in this population. 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 levels 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. 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). The mean level of spike-specific IgG increased from 1620 (SD, 3460) to 8772 (SD, 16733) AU/ml (p<0·0001). Serum neutralizing activity increased after the third dose for all variants of concern tested including the Delta variant (p<0·0001). The frequency of spike-specific 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 cross-variant neutralizing antibody and cellular responses in KT recipients with an acceptable tolerability profile. Funding: Nice University Hospital, University Cote d'Azur. |
| format |
article |
| author |
Filippo Massa, PhD Marion Cremoni, MD Alexandre Gérard, MD Hanen Grabsi Lory Rogier Mathilde Blois, MD Chloé Couzin, MD Nadia Ben Hassen Matthieu Rouleau, PhD Susana Barbosa, PhD Emanuela Martinuzzi, PhD Julien Fayada Ghislaine Bernard, MD-PhD Guillaume Favre, MD-PhD Paul Hofman, MD-PhD Vincent L.M. Esnault, MD-PhD Cecil Czerkinsky, MD-PhD Barbara Seitz-Polski, MD-PhD Nicolas Glaichenhaus, PhD Antoine Sicard, MD-PhD |
| author_facet |
Filippo Massa, PhD Marion Cremoni, MD Alexandre Gérard, MD Hanen Grabsi Lory Rogier Mathilde Blois, MD Chloé Couzin, MD Nadia Ben Hassen Matthieu Rouleau, PhD Susana Barbosa, PhD Emanuela Martinuzzi, PhD Julien Fayada Ghislaine Bernard, MD-PhD Guillaume Favre, MD-PhD Paul Hofman, MD-PhD Vincent L.M. Esnault, MD-PhD Cecil Czerkinsky, MD-PhD Barbara Seitz-Polski, MD-PhD Nicolas Glaichenhaus, PhD Antoine Sicard, MD-PhD |
| author_sort |
Filippo Massa, PhD |
| title |
Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients |
| title_short |
Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients |
| title_full |
Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients |
| title_fullStr |
Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients |
| title_full_unstemmed |
Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients |
| title_sort |
safety and cross-variant immunogenicity of a three-dose covid-19 mrna vaccine regimen in kidney transplant recipients |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/6aec33f0dd6e4ddba8069d07e0e047f1 |
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