Author:
Dowell Alexander C.,Powell Annabel A.,Davis Chris,Scott Sam,Logan Nicola,Willett Brian J.,Bruton Rachel,Ayodele Morenike,Jinks Elizabeth,Gunn Juliet,Spalkova Eliska,Sylla Panagiota,Nicol Samantha M.,Zuo Jianmin,Ireland Georgina,Okike Ifeanyichukwu,Baawuah Frances,Beckmann Joanne,Ahmad Shazaad,Garstang Joanna,Brent Andrew J.,Brent Bernadette,White Marie,Collins Aedin,Davis Francesca,Lim Ming,Cohen Jonathan,Kenny Julia,Linley Ezra,Poh John,Amirthalingam Gayatri,Brown Kevin,Ramsay Mary E.,Azad Rafaq,Wright John,Waiblinger Dagmar,Moss Paul,Ladhani Shamez N.
Abstract
Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant.
Subject
Immunology,Immunology and Allergy