Functional T cell response to COVID-19 vaccination with or without natural infection with SARS-CoV-2 in adults and children

Abstract

Severe COVID-19 is rare in children suggesting differences in immune response between children and adults. Limited information is available on how cellular immunity is modulated by COVID-19 vaccination and prior infection, and whether it is differentially modulated in children compared to adults. Here, we aimed to compare COVID-19 vaccine-induced functional T cell response between adults and children with and without previous SARS-CoV-2 infection. Adults (18-45 years; n = 45) and children (5-10 years; n = 51;), who received Pfizer-BioNTech COVID-19 vaccine or remained unvaccinated, and previously infected or not with SARS-CoV-2 were selected from two cross-sectional SARS-CoV-2 serosurveillance studies conducted in Bangladesh. Plasma nucleocapsid (N)-specific antibodies were measured by electrochemiluminescence immunoassay; IFN-γ, perforin and granzyme B secreting T cells were assessed using ELISpot assay. Vaccination in adults without previous infection, induced higher frequencies of IFN-γ and granzyme B secreting T lymphocytes compared to unvaccinated adults, while it increased only IFN-γ expression in vaccinated children. Previous infection increased IFN-γ response in unvaccinated adults only. Unvaccinated children showed higher granzyme B expression compared to adults irrespective of infection status. In vaccinated individuals, prior infection induced perforin expression in both adults and children. Children showed slightly different functional T cell response than adults in response to COVID-19 vaccination and infection. mRNA vaccination provided higher IFN-γ response in both adults and children, but induced cytotoxic T lymphocyte (CTL) response in adults only. Future studies may evaluate the impact of other types of COVID-19 vaccines on functional T cell immunity in children to confirm the findings.

Keywords: Cellular immunity; Cytotoxic T lymphocyte; Granzyme B; IFN-γ; Perforin.

Fig. 1

Flow Chart describing the selection of study participants.

Fig. 2

Comparison of IFN-γ and cytotoxic granule molecule secreting T cell responses between vaccinated and unvaccinated participants among uninfected individuals stratified by age. Plot (A) denotes all uninfected participant including both adults and children (red thatched and white bars), plot (B) denotes uninfected adult group (green and white bars), Plot (C) denotes uninfected children group (blue and white bars). Data were log-transformed and reported as geometric mean (back-transformed) with standard deviation. An independent t-test was conducted to calculate the p-value.

Fig. 3

Comparison of cytotoxic granule molecules and IFN-γ secreting T cell responses between infected and uninfected participants among unvaccinated (plots A and C) and vaccinated (plots B and D) ones. Green with white bars denote adults (Left panel) and blue with white bars denote children (right panel). Data were log-transformed and reported as geometric mean (back-transformed) with standard deviation. An independent t-test was conducted to calculate the p-value.