The ROMANOV study found impaired humoral and cellular immune responses to SARS-CoV-2 mRNA vaccine in virus-unexposed patients receiving maintenance hemodialysis

Espi, M.; Charmetant, Xavier; Barba, Thomas; Koppe, Laetitia; Pelletier, C.; Kalbacher, Emilie; Chalencon, É.; Mathias, Virginie; Ovize, Anne; Cart-Tanneur, Emmanuelle; Bouz, Christine; Pellegrina, Laurence; Morélon, Emmanuel; Fouque, Denis; Juillard, Laurent; Thaunat, Olivier

doi:10.1016/j.kint.2021.07.005

Cited by 71 publications

(85 citation statements)

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“…The spike glycoprotein mediates virus entry into target cells via the ACE2 receptor and it has been shown that antibodies directed against the RBD can block viral infection of human cells in vitro and counter viral replication in vivo (26)(27)(28)(29)(30). In line with these studies, and despite the fact that the titers were lower than those observed in a cohort of 30 vaccinated healthy volunteers (31), sera of infected transplant recipients still very efficiently block pseudo-virus entry in human cells in vitro (Figure 3C). A positive correlation between anti-RBD IgG titer and the result of the in vitro neutralization assay was demonstrated (Figure 3D).…”

Section: Presence Of Neutralizing Igg Correlates With Protection Against Covid-19 In Transplant Recipientsmentioning

confidence: 74%

Comparison of infected and vaccinated transplant recipients highlights the role of Tfh and neutralizing IgG in COVID-19 protection

Charmetant

Espi

Benotmane

et al. 2021

Preprint

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Transplant recipients, which receive therapeutic immunosuppression to prevent graft rejection, are characterized by high COVID-19-related mortality and defective response to vaccines. Having observed that previous infection by SARS-CoV-2 but not the standard 2 doses scheme of vaccination, provided complete protection against COVID-19 to transplant recipients, we undertook this translational study to compare the cellular and humoral immune responses of these 2 groups of patients. Neutralizing anti-Receptor Binding Domain (RBD) IgG were identified as the critical immune effectors associated with protection. Generation of anti-RBD IgG was dependent upon spike-specific T follicular helper (Tfh) CD4+ T cells, which acted as limiting checkpoint. Tfh generation was impeded by high dose mycophenolate mofetil in non-responders to vaccine but not in infected patients, suggesting that increasing immunogenicity of vaccine could improve response rate to mRNA vaccine. This theory was validated in two independent prospective cohorts, in which administration of a 3rd dose of vaccine resulted in the generation of anti-RBD IgG in half of non-responders to 2 doses.

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Section: Presence Of Neutralizing Igg Correlates With Protection Against Covid-19 In Transplant Recipientsmentioning

confidence: 74%

Comparison of infected and vaccinated transplant recipients highlights the role of Tfh and neutralizing IgG in COVID-19 protection

Charmetant

Espi

Benotmane

et al. 2021

Preprint

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“…Even though age might be a factor in the immune response it is hardly the sole explanation. In our patient cohort the mean age was 69.4 years, in the ROMANOV-study [ 9 ] 64.9, and in the three other studies, 67.6, 67.4, 71.2 and 68.6 years, respectively [ 10 – 13 ]. Perhaps differences in the assessment of the cellular response thus may the most important factor to consider and warrants further evaluate.…”

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

“…There are few studies that have addressed the cellular response to SARS-CoV-2 BNT162b2 mRNA vaccine in HD-patients [ 9 – 13 ]. In the ROMANOV study a decreased cellular response to the BNT162b2 vaccine was found [ 9 ]. In addition, three recent studies showed that the cellular response to the vaccine was slightly decreased in dialysis patients but to a lesser extent than in transplanted patients on triple immunosuppression therapy [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Humoral and cellular response to SARS-CoV-2 BNT162b2 mRNA vaccine in hemodialysis patients

et al. 2021

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Background Hemodialysis (HD) patients have an increased risk of acquiring infections due to many health care contacts and may, in addition, have a suboptimal response to vaccination and a high mortality from Covid-19 infection. Methods In 50 HD patients (mean age 69.4 years, 62% men) administration of SARS-CoV-2BNT162b2 mRNA vaccine began in Dec 2020 and the immune response was evaluated 7–15 weeks after the last dose. Levels of Covid-19 (SARS-CoV-2) IgG antibody against the nucleocapsid antigen (anti-N) and the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using ELISPOT technology were evaluated. Results Out of 50 patients, anti-S IgG antibodies indicating a vaccine effect or previous Covid-19 infection, were detected in 37 (74%), 5 (10%) had a borderline response and 8 (16%) were negative after two doses of vaccine. T-cell responses were detected in 29 (58%). Of the 37 patients with anti-S antibodies, 25 (68%) had a measurable T-cell response. 2 (40%) out of 5 patients with borderline anti-S and 2 (25%) without anti-S had a concomitant T-cell response. Twenty-seven (54%) had both an antibody and T-cell response. IgG antibodies to anti-N indicating a previous Covid-19 disease were detected in 7 (14%) patients. Conclusions Most HD patients develop a B- and/or T-cell response after vaccination against Covid-19 but approx. 20% had a limited immunological response. T-cell reactivity against Covid-19 was only present in a few of the anti-S antibody negative patients.

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“…Given their increased vulnerability to severe COVID-19, kidney transplant recipients need to be effectively vaccinated. Although kidney transplantation candidates receiving chronic haemodialysis also have a defective response to the COVID-19 mRNA vaccine 9 , this defect is milder than that observed in transplant recipients being treated with immunosuppressive drugs. COVID-19 vaccination should therefore be administered during the pre-transplant waiting period.…”

mentioning

confidence: 96%

COVID-19 vaccination in kidney transplant recipients

2021

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The ROMANOV study found impaired humoral and cellular immune responses to SARS-CoV-2 mRNA vaccine in virus-unexposed patients receiving maintenance hemodialysis

Abstract: The ROMANOV study found impaired humoral and cellular immune responses to SARSCov-2 mRNA vaccine in virus unexposed patients receiving maintenance hemodialysis.

Cited by 71 publications

References 20 publications

Comparison of infected and vaccinated transplant recipients highlights the role of Tfh and neutralizing IgG in COVID-19 protection

Comparison of infected and vaccinated transplant recipients highlights the role of Tfh and neutralizing IgG in COVID-19 protection

Humoral and cellular response to SARS-CoV-2 BNT162b2 mRNA vaccine in hemodialysis patients

COVID-19 vaccination in kidney transplant recipients

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