Predictive factors of a viral neutralizing humoral response after a third dose of COVID-19 mRNA vaccine

Charmetant, Xavier; Espi, M.; Barba, Thomas; Ovize, Anne; Morélon, Emmanuel; Mathieu, Cyrille; Thaunat, Olivier

doi:10.1111/ajt.16990

Cited by 18 publications

(20 citation statements)

References 44 publications

(106 reference statements)

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“…Given the poor rates of immunologic response, a three-dose regimen for immunocompromised individuals has been implemented, and was reported to be associated with a marked improvement in immunologic response in KT recipients [ 33 – 36 ]. In a French cohort of 78 adult KT recipients, SARS-COV-2 antibodies were detected in 40% of patients following the second dose compared to 68% following the third dose [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Immunologic response to SARS-CoV-2 mRNA vaccination in pediatric kidney transplant recipients

et al. 2022

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Background COVID-19 disease in kidney transplant (KT) recipients is associated with increased morbidity, mortality, and hospitalization rates. Unfortunately, KT recipients also have a reduced response to SARS-CoV-2 immunization. The primary aim of this study was to assess immunologic response to SARS-CoV-2 mRNA vaccines in pediatric kidney transplant recipients 12–18 years of age. Secondary aims were to assess response rates following a third immunization and determine factors that influence immunization response. Methods Pediatric KT recipients in a single tertiary center received SARS-CoV-2 mRNA vaccination as per local protocol. SARS-CoV-2 immunoglobulin (IgG) was measured following second and/or third vaccination. Demographics including patient factors (age, gender, and underlying disease), transplant factors (time and type of transplant), and immunosuppression (induction, maintenance, and immunomodulatory therapies such as IVIG) were collected from the medical records. Results Of 20 participants, 10 (50%) responded following a two-dose vaccine schedule, which increased to 15 (75%) after three doses. Maintenance immunosuppression affected immunologic response, with azathioprine demonstrating a higher rate of response to vaccine compared to mycophenolate (100% vs. 38%, p = 0.04). Increasing prednisolone dose had a negative impact on immunologic response (0.01 mg/kg/day increase: OR 1.60 95% CI 1.01 to 2.57). Tacrolimus dose and trough levels, age, time post-transplant, underlying disease, and other immunosuppression did not impact immunologic response. Conclusions Pediatric KT recipients had similar response rates following SARS-CoV-2 immunization as adult KT recipients. Immunologic response improved following a third immunization. Choice of antimetabolite and prednisolone dosing influenced the rate of response. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary Information Supplementary Information The online version contains supplementary material available at 10.1007/s00467-022-05679-y.

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Section: Discussionmentioning

confidence: 99%

Immunologic response to SARS-CoV-2 mRNA vaccination in pediatric kidney transplant recipients

et al. 2022

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“…Of note, in two studies that used flow cytometry, S-protein-reactive T cells were detected in 90% and 95%, respectively 137 , 139 . Importantly, detectable levels of anti-RBD IgG antibodies and S-protein-reactive CD4 + T cells were predictive of a high response to the third primary vaccine dose 131 . By contrast, <10% of patients with failed seroconversion and negative IFNγ-release assay responded to a third dose 131 .…”

Section: Strategies To Improve Vaccination Responsesmentioning

confidence: 96%

Vaccination in patients with kidney failure: lessons from COVID-19

2022

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Infection is the second leading cause of death in patients with chronic kidney disease (CKD). Adequate humoral (antibody) and cellular (T cell-driven) immunity are required to minimize pathogen entry and promote pathogen clearance to enable infection control. Vaccination can generate cellular and humoral immunity against specific pathogens and is used to prevent many life-threatening infectious diseases. However, vaccination efficacy is diminished in patients with CKD. Premature ageing of the immune system and chronic systemic low-grade inflammation are the main causes of immune alteration in these patients. In the case of SARS-CoV-2 infection, COVID-19 can have considerable detrimental effects in patients with CKD, especially in those with kidney failure. COVID-19 prevention through successful vaccination is therefore paramount in this vulnerable population. Although patients receiving dialysis have seroconversion rates comparable to those of patients with normal kidney function, most kidney transplant recipients could not generate humoral immunity after two doses of the COVID-19 vaccine. Importantly, some patients who were not able to produce antibodies still had a detectable vaccine-specific T cell response, which might be sufficient to prevent severe COVID-19. Correlates of protection against SARS-CoV-2 have not been established for patients with kidney failure, but they are urgently needed to enable personalized vaccination regimens.

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“… 16 In a French cohort study, lower posttransplant duration and high‐maintenance immunosuppression were found to be unfavorable predictors for seroconversion in KT recipients. 22 These parameters could be used to create a COVID‐19 immunization plan customized by individual immune status. The strategy of temporarily pausing immunosuppressant use has been proposed; however, allograft rejection is a barrier to implementing this practice, especially for those with high a immunologic risk or recent transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…16 In a French cohort study, lower posttransplant duration and highmaintenance immunosuppression were found to be unfavorable predictors for seroconversion in KT recipients. 22 vaccine types as a booster dose. 17 Some of our participants experienced more pain on the injected side after receiving the mRNA vaccine compared with the viral vector vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…KT recipients who were maintained on less than three immunosuppressive drugs are more likely to develop antibody responses, as are those with a longer posttransplant time 16 . In a French cohort study, lower posttransplant duration and high‐maintenance immunosuppression were found to be unfavorable predictors for seroconversion in KT recipients 22 . These parameters could be used to create a COVID‐19 immunization plan customized by individual immune status.…”

Section: Discussionmentioning

confidence: 99%

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An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study)

Bruminhent

Setthaudom

Phornkittikorn

et al. 2022

American Journal of Transplantation

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Immunogenicity following an additional dose of Coronavirus disease 2019 (COVID‐19) vaccine was investigated in an extended primary series among kidney transplant (KT) recipients. Eighty‐five KT participants were randomized to receive either an mRNA (M group; n = 43) or viral vector (V group; n = 42) vaccine. Among them, 62% were male, with a median (IQR) age of 50 (43–59) years and post‐transplantation duration of 46 (26–82) months. At 2 weeks post‐additional dose, there was no difference in the seroconversion rate between the M and V groups (70% vs. 65%, p = .63). A median (IQR) of anti‐RBD antibody level was not statistically different between the M group compared with the V group (51.8 [5.1–591] vs. 28.5 [2.9–119.3] BAU/ml, p = .18). Furthermore, the percentage of participants with positive SARS‐CoV‐2 surrogate virus neutralization test results was not statistically different between groups (20% vs. 15%, p = .40). S1‐specific T cell and RBD‐specific B cell responses were also comparable between the M and V groups (230 [41–420] vs. 268 [118–510], p = .65 and 2 [0–10] vs. 2 [0–13] spot‐forming units/10 6 peripheral blood mononuclear cells, p = .60). In conclusion, compared with an additional dose of viral vector COVID‐19 vaccine, a dose of mRNA COVID‐19 vaccine did not elicit significantly different responses in KT recipients, regarding either humoral or cell‐mediated immunity. (TCTR20211102003).

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Predictive factors of a viral neutralizing humoral response after a third dose of COVID-19 mRNA vaccine

Cited by 18 publications

References 44 publications

Immunologic response to SARS-CoV-2 mRNA vaccination in pediatric kidney transplant recipients

Immunologic response to SARS-CoV-2 mRNA vaccination in pediatric kidney transplant recipients

Vaccination in patients with kidney failure: lessons from COVID-19

An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study)

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