Humoral and cellular immune correlates of protection against COVID-19 in kidney transplant recipients

Kemlin, Delphine; Gemander, Nicolas; Depickère, Stéphanie; Olislagers, Véronique; Georges, Daphnée; Waegemans, Alexandra; Pannus, Pieter; Lemy, Anne; Goossens, Maria E.; Desombere, Isabelle; Míchiels, Johan; Vandevenne, Marylène; Heyndríckx, Leo; Ariën, Kevin K.; Matagne, André; Ackerman, Margaret E.; Moine, Alaín Le; Marchant, Arnaud

doi:10.1016/j.ajt.2023.02.015

Cited by 22 publications

(18 citation statements)

References 29 publications

(39 reference statements)

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Section: Discussionsupporting

confidence: 81%

“…They showed an insufficient humoral response to the booster vaccination schedule, including virus neutralization capacity assessment. These and previously published data support the importance of an adequate humoral response including virus neutralizing capacity in patients after kidney transplantation to protect against COVID-19 with a severe course 8. The main strength of this trial is the prospective, randomized design with direct comparison of the immunogenicity of one and two SARS-CoV-2 mRNA booster doses (administered 28 days apart) in kidney transplant recipients who remained seronegative after the previous two-dose vaccination schedule and at the time of the booster dose.The immunogenic potential of the two types of mRNA vaccines, either mRNA-1273 or BNT162b2, was also compared.…”

supporting

confidence: 82%

“…1,[5][6][7] However, it is questionable whether the level of cellular immunity induced by mRNA vaccine correlates with the degree of protection against COVID-19 in patients after kidney transplantation. 1,7,8 The third vaccine dose appears to enhance the antibody response, including virus neutralization capacity, but only in a subset of previously seronegative transplant recipients (33%-49%). [9][10][11][12][13] Homologous and heterologous adjuvant vaccination strategy of the third and fourth dose is safe and well tolerated.…”

Section: Introductionmentioning

confidence: 99%

“…In spite of the reduced humoral response, an increasing number of SARS‐CoV‐2 specific cells was observed after the second vaccination dose 1,5‐7 . However, it is questionable whether the level of cellular immunity induced by mRNA vaccine correlates with the degree of protection against COVID‐19 in patients after kidney transplantation 1,7,8 9‐13 .…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of one and two booster doses of SARS‐CoV‐2 mRNA vaccines in kidney transplant recipients: A randomized clinical trial

Drenko,

Kacer,

Kielberger

et al. 2023

Transplant Infectious Dis

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BackgroundKidney transplant recipients are at risk for a severe course of COVID‐19 with a high mortality rate. A considerable number of patients remains without a satisfactory serological response after the baseline and adjuvant SARS‐CoV‐2 vaccination schedule.MethodsIn this prospective, randomized study, we evaluated the efficacy and safety of one and two booster doses of mRNA vaccines (either mRNA‐1273 or BNT162b2) in 125 COVID‐19 naive, adult kidney transplant recipients who showed an insufficient humoral response (SARS‐CoV‐2 IgG <10 AU/ml) to the previous 2‐dose vaccination schedule. The primary outcome was the difference in the rate of a positive antibody response (SARS‐CoV‐2 IgG ≥10 AU/ml) between one and two booster doses at 1 month after the final booster dose.ResultsA positive humoral response was observed in 36 (62%) patients receiving two booster doses and in 28 (44%) patients receiving one booster dose (odds ratio [OR], 2.10, 95% confidence interval [CI], 1.02–4.34, p = .043). Moreover, median SARS‐CoV‐2 IgG levels were higher with two booster doses (p = .009). The number of patients with positive virus neutralizing antibody (VNA) levels was numerically higher with two booster doses compared to one booster dose, but without statistical significance (66% vs. 50%, p = .084). There was no significant difference in positive seroconversions rate and antibody levels between mRNA‐1273 and BNT162b2.ConclusionA higher number of kidney transplant recipients achieved a positive antibody response after two booster doses compared to one booster dose. image

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Section: Discussionsupporting

confidence: 81%

supporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of one and two booster doses of SARS‐CoV‐2 mRNA vaccines in kidney transplant recipients: A randomized clinical trial

Drenko,

Kacer,

Kielberger

et al. 2023

Transplant Infectious Dis

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“…However, this does not prove that antibodies are exclusively responsible for protection against severe disease, and we cannot exclude the possibility that there are alternate mechanisms, such as T-cells, that also contribute to protection. Some evidence has suggested a potential role for T-cell responses when neutralising antibody responses are not detected 43 . However, since cellular responses and neutralising antibodies typically correlate, it is difficult to determine whether T-cells are causal in this instance or merely correlated with a level of neutralising antibodies that is below assay detection 44 .…”

Section: Discussionmentioning

confidence: 99%

Predicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis

et al. 2023

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Vaccine protection from symptomatic SARS-CoV-2 infection has been shown to be strongly correlated with neutralising antibody titres; however, this has not yet been demonstrated for severe COVID-19. To explore whether this relationship also holds for severe COVID-19, we performed a systematic search for studies reporting on protection against different SARS-CoV-2 clinical endpoints and extracted data from 15 studies. Since matched neutralising antibody titres were not available, we used the vaccine regimen, time since vaccination and variant of concern to predict corresponding neutralising antibody titres. We then compared the observed vaccine effectiveness reported in these studies to the protection predicted by a previously published model of the relationship between neutralising antibody titre and vaccine effectiveness against severe COVID-19. We find that predicted neutralising antibody titres are strongly correlated with observed vaccine effectiveness against symptomatic (Spearman $$\rho$$ ρ = 0.95, p < 0.001) and severe (Spearman $$\rho$$ ρ = 0.72, p < 0.001 for both) COVID-19 and that the loss of neutralising antibodies over time and to new variants are strongly predictive of observed vaccine protection against severe COVID-19.

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Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: A national observational study in France

Leye,

Delory,

El Karoui

et al. 2024

American Journal of Transplantation

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Humoral and cellular immune correlates of protection against COVID-19 in kidney transplant recipients

Cited by 22 publications

References 29 publications

Safety and efficacy of one and two booster doses of SARS‐CoV‐2 mRNA vaccines in kidney transplant recipients: A randomized clinical trial

Safety and efficacy of one and two booster doses of SARS‐CoV‐2 mRNA vaccines in kidney transplant recipients: A randomized clinical trial

Predicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis

Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: A national observational study in France

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