Safety and cross-variant immunogenicity of a three-dose COVID-19 mRNA vaccine regimen in kidney transplant recipients

Massa, Filippo; Crémoni, Marion; Gérard, Alexandre O.; Grabsi, Hanen; Rogier, L.J.J.; Blois, M.-C. De; Couzin, Chloé; Hassen, Nadia Ben; Rouleau, Matthieu; Barbosa, Susana; Martinuzzi, Emanuela; Fayada, Julien; Bernard, Ghislaine; Favre, Guillaume; Hofman, Paul; Esnault, Vincent; Czerkinsky, Cécil; Seitz-Polski, Barbara; Glaichenhaus, Nicolas; Sicard, A

doi:10.1016/j.ebiom.2021.103679

Cited by 74 publications

(99 citation statements)

References 22 publications

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“…Our findings support the need of an additional boost, preferentially with a high-dose mRNA vaccine, in this population [62][63][64][65][66][67], which, however, need to be continuously monitored with proper serological tests that measure not only the serum antibody levels, but also their neutralizing activity, either directly or indirectly through an avidity test. Finally, our data suggest that some patients may not respond efficiently even after an additional boost and, therefore, in case of SARS-CoV-2 infection, they should be considered for other therapeutic strategies, including early immunotherapy with monoclonal antibodies.…”

Section: Discussionsupporting

confidence: 70%

Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

Bassi

Giannini

Silacci-Fregni

et al. 2021

Preprint

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Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis (HD) and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naive HD patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity, consistent with a delayed affinity maturation of SARS-CoV-2 S-specific B cells. These data indicate that dialysis patients should be considered for an additional boost and other therapeutic strategies, including early immunotherapy with monoclonal antibodies.

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Section: Discussionsupporting

confidence: 70%

Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

Bassi

Giannini

Silacci-Fregni

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In conclusion, our study demonstrates, at the functional level, that mRNA vaccines induce a poor neutralizing and rapidly decaying antibody response against SARS-CoV-2 variants in dialysis patients, in particular in naïve HD patients immunized with BNT162b2. Our findings support the need of an additional boost, preferentially with a high-dose mRNA vaccine, in this population [62][63][64][65][66][67], which, however, need to be continuously monitored with proper serological tests that measure not only the serum antibody levels, but also their neutralizing activity, either directly or indirectly through an avidity test. Finally, our data suggest that some patients may not respond efficiently even after an additional boost and, therefore, in case of SARS--CoV-2 infection, they should be considered for other therapeutic strategies, including early immunotherapy with monoclonal antibodies.…”

Section: Plos Onesupporting

confidence: 70%

Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

et al. 2022

View full text Add to dashboard Cite

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.

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“…Recent data in solid-organ transplant recipients showed that a third dose of BNT162b2 vaccine increased the prevalence of seroconversion and antibody titres, without serious adverse events. [25][26][27] A third dose also increased specific cellular response even in patients who remained seronegative, but the impact of this cellular response remains to be determined. 27 We analysed B-cell and T-cell responses at 6 months in 40% of our immunocompromised patients having received a third dose of vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…[25][26][27] A third dose also increased specific cellular response even in patients who remained seronegative, but the impact of this cellular response remains to be determined. 27 We analysed B-cell and T-cell responses at 6 months in 40% of our immunocompromised patients having received a third dose of vaccine. A third dose of vaccine had no effect on B-cell response in patients treated with rituximab but it significantly increased anti-spike IgG levels and neutralisation activity against both variants in patients with methotrexate and cDMARDs compared with those receiving only two doses.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

et al. 2022

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ObjectivesThe emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. We aimed to evaluate seroconversion, cross-neutralisation and T-cell responses induced by BNT162b2 in immunocompromised patients with systemic inflammatory diseases.MethodsProspective monocentric study including patients with systemic inflammatory diseases and healthcare immunocompetent workers as controls. Primary endpoints were anti-spike antibodies levels and cross-neutralisation of Alpha and Delta variants after BNT162b2 vaccine. Secondary endpoints were T-cell responses, breakthrough infections and safety.ResultsSixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analysed. Kinetics of anti-spike IgG after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralising response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralised Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralising activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after two doses of BNT162b2. Third dose of vaccine improved immunogenicity in patients with low responses.ConclusionRituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals (ClinicalTrials.gov number, NCT04870411).

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Safety and cross-variant immunogenicity of a three-dose COVID-19 mRNA vaccine regimen in kidney transplant recipients

Cited by 74 publications

References 22 publications

Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

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