Optimizing COVID-19 Vaccination Strategy in Pediatric Kidney Transplant Recipients: Humoral and Cellular Response to SARS-CoV-2 mRNA Vaccination

Abstract

In this retrospective cohort study, we analyze the early humoral and cellular response in 64 adolescents KTx recipients, after two or three doses of mRNA vaccine BNT162b2 against different variants of COVID-19. After 2 doses, 77.8% % of children with no history of infection had a positive humoral response with a median anti-S IgG level of 1107 (IQR, 593-2,658) BAU/mL. All the patients with a history of infection responded with a higher median IgG level (3,265 (IQR, 1,492-8,178) BAU/mL). In non-responders after 2 doses, 75% responded after a third dose with a median Ab titer at 355 (IQR, 140-3,865 BAU/mL). Neutralizing activity was significantly lower against the delta and the omicron variants compared to the wild-type strain and did not improve after a 3rd dose, while infection did provide higher levels of neutralizations against the variants. T cell specific response correlated with humoral response and no patient displayed a cellular response without a humoral response. Adolescent KTx recipients exhibit a high seroconversion rate after only two doses. A third injection, induces a response in the majority of the non-responders patients but did not counterbalance the strong decrease in neutralizing antibody activities against variants highlighting the need for boosters with specific vaccines.

Keywords: COVID-19; children; immunology; kidney transplantation; pediatric.

FIGURE 1

Study design: Study population flow-chart (A) and immunological assays (B).

FIGURE 2

Antibody response to SARS-CoV-2 following two or three injections of SARS-CoV-2 mRNA vaccine in KTx children. (A) Titers of anti-S IgG are shown in 32 KTx children following two injections of SARS-CoV-2 mRNA vaccine. Children are classified according to their history of previous natural SARS-CoV-2 infection before the second injection: with natural infection (I) or without natural infection (NI). (B) Antibody titers to SARS-CoV-2 following three injections of SARS-CoV-2 mRNA vaccine in 40 KTx children classified according to their humoral response following the second vaccine injection: Responder (R) for positive response, Non-responder (NR) for negative response and Unclassified (NC) for children with missing data. (C) Matched SARS-CoV-2 antibody titers for eight patients following the second and third vaccine doses. Dashed horizontal lines represent the threshold of positive humoral response (33.8 BAU/mL) and the ab level associated with 80% of vaccine efficacy against primary symptomatic COVID-19 (264 BAU/mL). Medians and interquartile ranges are shown.

FIGURE 3

Neutralizing antibody responses against wild-type, Delta and Omicron SARS-CoV-2 strains following two or three injections of SARS-CoV-2 mRNA vaccine in KTx children. (A) Neutralizing antibody activities against SARS-CoV-2 strains following two injections of SARS-CoV-2 mRNA vaccine classified according to their previous natural SARS-CoV-2 infection before the second injection: with natural infection (I) or without natural infection (NI). (B) Neutralizing antibody activities against SARS-CoV-2 strains following three injections of SARS-CoV-2 mRNA vaccine. Children are classified according to their humoral response following the second vaccine injection: Responder (R) for positive response, Non-responder (NR) for negative response and Unclassified (NC) for children with missing data. (C) Matched SARS-CoV-2 antibody neutralizing activities against SARS-CoV-2 strains for eight KTx children following the second and third vaccine doses. Dashed horizontal lines represent the threshold of positive neutralizing antibody response (30%). Medians and interquartile ranges are shown. Anti-SARS-CoV-2 neutralizing antibody activities were evaluated against the wild-type (WT) strain and the Delta and Omicron variants. Medians and interquartile ranges are shown.

FIGURE 4

Correlation of anti-S IgG titers and neutralizing antibody activities against the wild-type strain, Delta and Omicron variants of SARS-CoV-2 in KTx children. Correlation of anti-S IgG titers and neutralizing antibody activities against the wild-type strain (WT) (A), Delta (B) and Omicron (C) strain in 71 KTx children (31 following two injections and 40 following three injections). Dashed lines represent the threshold of positive humoral response (33.8 BAU/mL) and the threshold of positive neutralizing antibody response (30%).

FIGURE 5

Spike specific T cellular response following two or three injections of SARS-CoV-2 mRNA vaccine in KTx children. (A) SARS-CoV-2 specific T cell test results from top to bottom: negative control, anti-S T cell response, anti-N T cell response and positive control. (B) Numbers of anti-S T cells are shown in 28 KTx children following two injections of SARS-CoV-2 mRNA vaccine. Children are classified according to their previous natural SARS-CoV-2 infection before the second injection: with natural infection (I) or without natural infection (NI). Numbers of anti-S T cells following three injections of SARS-CoV-2 mRNA vaccine in 23 KTx children classified according to their humoral response following the second vaccine injection: Responder (R) for positive response, Non-responder (NR) for negative response and Unclassified (NC) for children with missing data. Medians and interquartile ranges are shown. (C) Correlation of anti-S humoral response and anti-S T cell response in 51 KTx children (28 KTx following two injections and 23 following three injections).