SARS-CoV2 mRNA Vaccine-Specific B-, T- and Humoral Responses in Adolescents After Kidney Transplantation

Abstract

Protection of adult kidney transplant recipients against SARS-CoV2 was shown to be strongly impaired owing to low reactogenicity of available vaccines. So far, data on vaccination outcomes in adolescents are scarce due to later vaccination approval for this age group. We therefore comprehensively analyzed vaccination-specific humoral-, T- and B-cell responses in kidney transplanted adolescents aged 12–18 years in comparison to healthy controls 6 weeks after standard two-dose BNT162b2 (“Comirnaty”; Pfizer/BioNTech) vaccination. Importantly, 90% (18/20) of transplanted adolescents showed IgG seroconversion with 75% (15/20) developing neutralizing titers. Still, both features were significantly diminished in magnitude compared to controls. Correspondingly, spike-specific B cells were quantitatively reduced and enriched for non-isotype-class-switched IgD+27+ memory cells in patients. Whereas spike specific CD4+ T cell frequencies were similar in both groups, cytokine production and memory differentiation were significantly impaired in transplant recipients. Although our data identify limitations in all arms of vaccine-specific immunity, the majority of our adolescent patients showed robust humoral responses despite antimetabolite-based treatment being associated with poor vaccination outcomes in adults.

Immunogenicity, Safety, and Clinical Effectiveness After 2 Doses of BNT162b2 Vaccine Among Pediatric Kidney Transplant Recipients Versus Healthy Volunteers: A Prospective Nonrandomized Study

“…The interval between vaccination and serological evaluation was different in the 2 groups, which may have interfered with the comparison of antibody values. The proportion of patients on mycophenolate was smaller than in previous studies, 4,5 limiting the generalizability of the data.…”

Immunogenicity, effectiveness, and safety of COVID-19 vaccines among children and adolescents aged 2–18 years: an updated systematic review and meta-analysis

“…Of the 88 articles included, there were 12 RCTs, two non-randomized clinical trials, 40 cohort studies, 19 cross-sectional studies, and 15 case-control studies. In the studies included, 16 articles were available for immunogenicity analysis (Supplementary Table 2) [14,15,18,[31][32][33][34][35][36][37][38][39][40][41][42][43]; 38 articles were available for effectiveness analysis (Supplementary Table 3) [14,17,19,31,; and 49 articles were available for safety analysis (Supplementary Table 4) [14-16, 18, 20-24, 31, 34, 35, 37, 41, 43, 45, 47, 50, 55, 78-107]. Children and adolescents are involved in 27 countries, including the United States, China, Australia, Argentina, Italy, Israel, France, Denmark, and South Korea, which have larger cohorts (> 100,000 people).…”

The humoral immune response to the BNT 162B2 vaccine in pediatrics on renal replacement therapy

“…The current published data showed variable humoral immune responses after the COVID‐19 vaccine in kidney transplant recipients with seroconversion rates as high as 91% and as low as 50% after the second dose 15–19 …”

“…Similar to previous reports, receiving mycophenolate as maintenance therapy and a short time from transplantation were associated with a negative response. 19 Children in the KTH group had a 100% seroconversion rate with SARS-CoV-2 IgG antibody titers that were 25-fold higher than the KTV group titers [370 AU/mL (240-400) vs. 15 (3.8-104), p < .005].…”