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Influenza B viruses (IBVs) cause substantive morbidity and mortality, and yet immunity towards IBVs remains understudied. CD8+ T-cells provide broadly cross-reactive immunity and alleviate disease severity by recognizing conserved epitopes. Despite the IBV burden, only 18 IBV-specific T-cell epitopes restricted by 5 HLAs have been identified currently. A broader array of conserved IBV T-cell epitopes is needed to develop effective cross-reactive T-cell based IBV vaccines. Here we identify 9 highly conserved IBV CD8+ T-cell epitopes restricted to HLA-B*07:02, HLA-B*08:01 and HLA-B*35:01. Memory IBVspecific tetramer+ CD8+ T-cells are present within blood and tissues. Frequencies of IBV-specific CD8+ T-cells decline with age, but maintain a central memory phenotype. HLA-B*07:02 and HLA-B*08:01-restricted NP30-38 epitopespecific T-cells have distinct T-cell receptor repertoires. We provide structural basis for the IBV HLA-B*07:02-restricted NS1196-206 (11-mer) and HLA-B*07:02- restricted NP30-38 epitope presentation. Our study increases the number of IBV CD8+ T-cell epitopes, and defines IBV-specific CD8+ T-cells at cellular and molecular levels, across tissues and age. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusions and Clinical Relevance The beneficial off‐target effects of Bacille Calmette–Guérin (BCG) vaccination potentially include protection against allergy.In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants.In this randomised controlled trial, 1272 neonates were allocated to BCG‐Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3‐monthly online questionnaires and oral food challenges. Data were analysed by intention‐to‐treat using binary regression. Clinicaltrials.gov (NCT01906853).Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI −1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI −3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration).Neonatal BCG‐Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life. [ABSTRACT FROM AUTHOR]

Influenza B viruses (IBVs) cause substantive morbidity and mortality, and yet immunity towards IBVs remains understudied. CD8 + T-cells provide broadly cross-reactive immunity and alleviate disease severity by recognizing conserved epitopes. Despite the IBV burden, only 18 IBV-specific T-cell epitopes restricted by 5 HLAs have been identified currently. A broader array of conserved IBV T-cell epitopes is needed to develop effective cross-reactive T-cell based IBV vaccines. Here we identify 9 highly conserved IBV CD8 + T-cell epitopes restricted to HLA-B*07:02, HLA-B*08:01 and HLA-B*35:01. Memory IBV-specific tetramer + CD8 + T-cells are present within blood and tissues. Frequencies of IBV-specific CD8 + T-cells decline with age, but maintain a central memory phenotype. HLA-B*07:02 and HLA-B*08:01-restricted NP 30-38 epitope-specific T-cells have distinct T-cell receptor repertoires. We provide structural basis for the IBV HLA-B*07:02-restricted NS1 196-206 (11-mer) and HLA-B*07:02-restricted NP 30-38 epitope presentation. Our study increases the number of IBV CD8 + T-cell epitopes, and defines IBV-specific CD8 + T-cells at cellular and molecular levels, across tissues and age., (© 2024. The Author(s).)