BNT162b2 vaccine induced variant-specific immunity, safety and risk of Omicron breakthrough infection in children aged 5 to 11 years: a cohort study

Abstract

There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) vaccination cohort study of healthy children 5-11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and spike-specific T cell responses against SARS-CoV-2 variants were performed. The mean age of 127 participants was 8.27 years (SD 1.95) and 51.2% were males. The median sVNT level against original variant after 1 dose and 2 dose vaccination was 61.4% and 95.1% respectively (p < 0.0001). Neutralizing antibodies against the Omicron variant was the lowest, median 22.4% (IQR 16.5-30.8). However, T cell IFN-γ cytokine response against Omicron variant was high and remained so about 4 months after vaccination. Fever rate increased significantly from 4% (dose 1) to 11.5% (dose 2). The risk of Omicron breakthrough infection decreased by 7.8% for every 1% increase in sVNT inhibition level measured after dose 2 vaccination. BNT162b2 vaccines were safe, induced good T cell responses but poor neutralizing antibodies against Omicron in children. Low neutralizing antibody levels post-vaccination was predictive of subsequent breakthrough infection.

Figure 1

Surrogate virus neutralization test (sVNT) after vaccination in children 5–11 years. (A) Distribution of sVNT at visit 1 (Day 0), 2 (Day 21), 3 (Day ~50) and 4 (Day ~120). (B) Vaccine induced sVNT against SARS-CoV-2 variants after the second dose at Visit 3 (Day ~50) in 5–11 years children.

Figure 2

Spike-specific T cell responses in vaccinated children. (A) IFN-γ secretion profile of whole-blood cultures stimulated with Spike protein peptide pool compared at different time points of paired samples from vaccinated individuals (n = 28). The limit of detection for IFN‐γ = 1.7 pg/ml. Values below limit of detection levels were plotted as 1. The mean values of each group are represented by a red line and were at visit 1, 2, 3 and 4: 1.7 pg/ml, 13.3 pg/ml, 64.8 pg/ml and 33.8 pg/ml of IFN‐γ, respectively. (B) PBMC of 5–11 years old children (n = 28) were tested on day 49 for their ability to respond to the Omicron variant of SARS-CoV-2 using IFN-γ ELISpot assays. Bars represent each individual; pie chart shows the mean reduction in the T cell response to Omicron.

Figure 3

Kaplan–Meier plot of neutralizing antibodies (sVNT) post dose 1 (A) and dose 2 (B) versus time to SARS-CoV-2 infection.