Oral Presentation Lorne Infection and Immunity 2022

SARS-CoV-2 infection in children does not necessitate establishment of adaptive SARS-CoV-2-specific immunological memory (#27)

Louise Rowntree 1 , Oanh Nguyen 1 , Lukasz Kedzierski 1 2 , Melanie Neeland 3 4 , Jan Petersen 5 6 , Jeremy Crawford 7 , Lilith Allen 1 , Anastasia Minervina 7 , Mikhail Pogorelyy 7 , Priyanka Chaurasia 5 , Hyon Xhi Tan 1 , Adam Wheatley 1 8 , Hayley McQuilten 1 , Bridie Clemens 1 , Fatima Amanat 9 10 , Florian Krammer 9 , Sabrina Sonda 11 , Katie Flanagan 11 12 13 14 , Paul Licciardi 3 4 , Stephen Kent 1 8 15 , Jamie Rossjohn 5 6 16 , Paul Thomas 7 , Shidan Tosif 3 4 17 , Nigel Crawford 3 18 , Carolien van de Sandt 1 , Katherine Kedzierska 1
  1. Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
  2. Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, Australia
  3. Infection and Immunity, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  4. Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia
  5. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
  6. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia
  7. Department of Immunology, St Jude Children’s Research Hospital, Memphis, Tennessee, USA
  8. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia
  9. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA
  10. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA
  11. School of Health Sciences and School of Medicine, University of Tasmania, Launceston, Tasmania, Australia
  12. Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia
  13. School of Health and Biomedical Science, RMIT University, Melbourne, Victoria, Australia
  14. Tasmanian Vaccine Trial Centre, Clifford Craig Foundation, , Launceston General Hospital, Launceston, Tasmania, Australia
  15. Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Central Clinical School, , Monash University, Melbourne, Victoria, Australia
  16. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
  17. Department of General Medicine, Royal Children’s Hospital Melbourne, Melbourne, Victoria, Australia
  18. Royal Children's Hospital Melbourne, Immunisation Service, Melbourne, Victoria, Australia

Children are at lower risk of developing severe COVID-19, yet the underlying immune mechanisms are understudied. While children’s innate immunity can drive rapid resolution of SARS-CoV-2 infection, the establishment of SARS-CoV-2-specific T-cell and B-cell memory in mild COVID-19 in children remains unexplored. We recruited a household cohort to understand SARS-CoV-2-specific CD4+ and CD8+ T-cell immune responses at one month after mild SARS-CoV-2 infection in PCR-positive children, in comparison to their mothers. We analysed SARS-CoV-2-specific T-cell responses, together with B-cells, directly ex vivo using six SARS-CoV-2 T-cell HLA class-I tetramers (A1/ORF1a1637, A2/S269, A3/N361, A24/S1208, B7/N105, B40/N322), one class-II tetramer (DPB4/S167), and Spike- and Receptor Binding Domain (RBD)-specific B-cell probes. Our in-depth profiling of epitope-specific T-cell responses at quantitative, phenotypic and clonal levels found that only children who seroconverted had prominent memory T-cell and B-cell profiles. These children had a high magnitude of SARS-CoV-2-specific T-cells displaying memory phenotypes and prevalent T cell receptor motifs, which were not observed in RBD IgG- but PCR+ children. This suggests that seroconversion but not PCR-positivity defines establishment of adaptive SARS-CoV-2-specific immunological memory in children, which is in contrast to adults with a mild SARS-CoV-2 infection. SARS-CoV-2-specific CD8+ and CD4+ T-cell responses in RBD IgG+ children were comparable to those of their mothers, with more prominent tetramer-specific T-cell responses associated with seropositivity rather than PCR status alone. Our study suggests that COVID-19 vaccination of children with mRNA vaccines could be a major advantage in terms of establishing T-cell and B-cell immunological memory.