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

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.