Poster Presentation 16th Lorne Infection and Immunity 2026

Bias for inducing IFN-γ vs IL-10 from T cells by specific peptides from SARS-CoV-2: optimising detection and biological implications (132562)

Kirsty Wilson 1 , Jack Jerome 1 , Georgia Goodchild 1 , Joshuah Fialho 1 , Monica Prakash 1 , Charlie McLeod 2 3 4 5 , Peter Richmond 2 5 6 7 , Katie Flanagan 8 9 10 , Magdalena Plebanski 1
  1. School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia
  2. Wesfarmers Centre of Vaccines and Infectious Diseases, Kids Research Institute of Australia, Nedlands, WA, Austrlaia
  3. Centre for Child Health Research, University of Western Australia, Crawley, WA, Australia
  4. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
  5. Infectious Diseases Department, Perth Children’s Hospital, Nedlands, WA, Australia
  6. Division of Paediatrics, University of Western Australia School of Medicine, Nedlands, WA, Australia
  7. Department of Immunology, Perth Children’s Hospital, Nedlands, WA, Australia
  8. Tasmanian Vaccine Trial Centre, Clifford Craig Foundation, Launceston General Hospital, Launceston, Tas, Australia
  9. School of Health Sciences and School of Medicine, University of Tasmania, Launceston, Tas, Australia
  10. Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, NSW, Australia

Understanding the balance of immune-stimulatory and immune-suppressive antigen specific responses to SARS-CoV-2 antigens is crucial for gaining insight into COVID-19 pathology, as well as for designing effective vaccine strategies. T cell responses to the SARS-CoV-2 Spike protein have proven to be long-lasting and protective in some human vaccine clinical trials. The Enzyme Linked Immuno Spot (ELISpot) assay is a powerful and sensitive tool to study antigen specific functional T cell responses. By using the Fluorospot method of the ELISpot, which incorporates multiple fluorescent readouts, we can not only assess individual T cell reactivity but also distinguish between immune-stimulating and immune-modulatory or suppressive responses by simultaneously measuring IFN-γ and IL-10. Preference for IFN-γ or IL-10 induction to Spike antigens could affect the overall strength, and protective potential, of vaccine induced responses. T cell responses to Spike ancestral and variant peptide pools (including novel and cross-reactive T cell epitope regions) were optimised in healthy blood donors using duo-colour Fluorospot assay. Donor specific IFN-γ responses were observed to both CD8 and CD4  peptide pools. Surprisingly, there was a preferential IL-10 induction to specific CD4 T cell epitopes within the pools, suggesting an intrinsically immunosuppressive bias. Immunogenicity to Spike peptide pools were optimised in healthy blood bank donors, and further studies will examine vaccine induced T cell responses in the Platform Trial In COVID-19 vaccine BOOsting clinical trial (PICOBOO), which aims to evaluate the effectiveness, safety, reactogenicity and immunogenicity of different booster vaccination strategies against SARS-CoV-2 ancestral and variant strains in the Australian population. Understanding the vaccine induced immune response to optimised SARS-CoV-2 Spike peptide epitope pools, with an intrinsic biological IFN-γ or IL10 induction bias, will further our knowledge of antigen-specific and cross-reactive immune-modulation by SARS-CoV-2 antigens and help inform future booster vaccination strategies.