Anti-SARS-CoV-2 Revaccination Success in Kidney Transplant Recipients With No Initial Humoral Response Is Linked to Primary Vaccine Type

Abstract

BackgroundWhile anti-SARS-CoV-2 vaccination success in kidney transplant recipients (KTR) after two doses and 1273-mRNA was associated with higher seroconversion rates compared to BNT162b2-mRNA in our “DIA-Vacc Study” (NCT04799808), it remains unclear whether this may also be the case in non-responding KTR after a third vaccination dose.Materials and MethodsNon-responding KTR (after two mRNA vaccinations) were investigated 4.5–6 months after study enrollment at first vaccination. One hundred sixty-six of 193 received a third vaccination between 3.5 and 5 months after the initial study enrollment and were always investigated 4 weeks later, exploring humoral immune response (ELISA) and specific cellular responses (interferon-γ release assay). Sixty-seven of 193 measurements in KTR were done immediately before the third vaccination or in KTR without further vaccination at 4.5–6 months.ResultsOf 193 KTR with no initial immune response 4 weeks after the second vaccination, 106/87 were immunized twice with 1273-mRNA/BNT162b2-mRNA, respectively. Additional mRNA booster vaccination led to positive seroconversion rates of 30–50%, while 16% of the initial non-responders demonstrated a delayed seroconversion without any booster vaccination. Using logistic regression analysis, a positive IgG response after the third vaccination was 23% more likely if the primary vaccine type was 1273-mRNA compared to BNT162b2-mRNA (OR = 4.420, 95% CI [1.208–16.173], p = 0.025). Primary vaccine type, a weak anti-SpikeS1 IgG response 4 weeks after second vaccination (3.2–35.2 BAU/ml, p < 0.001) and a lack of MMF/MPA as part of the immunosuppressive treatment (trend, p = 0.06) but no other variables studied correlated with seroconversion success.ConclusionThis observational study adds important evidence toward using 1273-mRNA as the primary mRNA vaccine type for immunosuppressed KTR.

Immunogenicity of mRNA-1273 and BNT162b2 in Immunocompromised Patients: Systematic Review and Meta-analysis Using GRADE

“…Type 3 due to nonrandomized studies j I 2 = 53.2%, Χ 2 = 12.81, p ( Q ) = 0.05; moderate heterogeneity k Wide 95% CI due to wide IQR and range for mean antibody levels per arm in Andreica et al [ 83 ] and Manjappa et al [ 85 ] l Lower grading due to imprecision and nonrandomized studies. No strong association identified, therefore type 4 m I 2 = 76.2%, Χ 2 = 54.56, p ( Q ) = 0; considerable heterogeneity n Wide 95% CI due to wide IQR for mean antibody levels per arm in Stumpf et al [ 75 ]…”

“…Type 3 due to nonrandomized studies j I 2 = 53.2%, Χ 2 = 12.81, p(Q) = 0.05; moderate heterogeneity k Wide 95% CI due to wide IQR and range for mean antibody levels per arm in Andreica et al [83] and Manjappa et al [85] l Lower grading due to imprecision and nonrandomized studies. No strong association identified, therefore type 4 m I 2 = 76.2%, Χ 2 = 54.56, p(Q) = 0; considerable heterogeneity n Wide 95% CI due to wide IQR for mean antibody levels per arm in Stumpf et al [75] GRADE analysis found that the certainty of evidence of the seroconversion outcome overall and in the solid organ transplant and autoimmunity subgroups was downgraded to type 4 (very low) due to imprecision and indirectness because different assays and antibody thresholds were used to assess and define seroconversion across the studies analyzed. Evidence certainty in the subgroup of patients with hematologic malignancies was retained as type 3 (i.e., the maximum certainty possible for nonrandomized studies), because there was a strong association in seroconversion likelihood and no issues with imprecision.…”

“…Most studies evaluated the 2-dose primary series (n = 81, 82.7%). Patients received 2 doses of the primary series followed by 1 booster dose in 17 studies (17.3%) [66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82]. Most studies did not specify whether the mRNA-1273 booster dose was a true booster (i.e., 50 mcg mRNA/dose) or a third dose of the primary series (i.e., 100 mcg mRNA/dose).…”

Cellular immune response of SARS-CoV-2 vaccination in kidney transplant recipients: a systematic review and meta-analysis

“…Four studies directly compared cellular immune responses in kidney transplant recipients vaccinated with mRNA versus the viral vector vaccine (34,42,43,53). Although comparison was not significant at <0.05, the pooled effect sizes and 95%CI for both two-and three-dose regimens demonstrated higher cellular immune response rates in kidney transplant recipients who received mRNA versus viral vector vaccines (Supplementary Figure S6).…”

“…Although comparison was not significant at <0.05, the pooled effect sizes and 95%CI for both two-and three-dose regimens demonstrated higher cellular immune response rates in kidney transplant recipients who received mRNA versus viral vector vaccines (Supplementary Figure S6). Three studies performed head-to-head comparisons of BNT162b2 and mRNA-1273, two after a single dose and a complete primary vaccination series (25, 31) and one after a booster dose (53), which did not show a significant difference of cellular immune responses between these mRNA vaccines.…”