ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Can Neonatal BCG Vaccination Provide Off-Target Protection Against Respiratory Tract Infections In Infants: Results From The MIS BAIR Randomised Controlled Trial (#270)

Nicole L Messina 1 2 , Laure F Pittet 1 2 3 , Kaya Gardiner 1 4 , Bridget Freyne 1 4 5 , Kate L Francis 6 , Christel Zufferey 1 , Veronica Abruzzo 1 , Clare Morrison 1 , Katrina J Allen 7 , Katie L Flanagan 8 9 10 , Anne-Louise Ponsonby 2 11 , Roy Robins-Browne 1 12 , Frank Shann 2 , Mike South 1 13 , Peter Vuillermin 11 14 15 , Susan Donath 2 6 , Dan Casalaz 16 , Nigel Curtis 1 2 3
  1. Infection, Immunity and Global Health theme, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
  2. Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia
  3. Infectious Diseases Unit, The Royal Children’s Hospital Melbourne, Parkville, Victoria, Australia
  4. Department of Research Operations, The Royal Children's Hospital, Parkville, Victoria, Australia
  5. Institute of Infection & Global Health University of Liverpool & Malawi-Liverpool Wellcome Trust Research Programme, Liverpool, UK
  6. Clinical Epidemiology & Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia
  7. Formerly of Centre for Food and Allergy Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia
  8. School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia
  9. School of Health and Biomedical Science, RMIT University, Melbourne, Victoria, Australia
  10. Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia
  11. Population Allergy, Murdoch Children's Research Institute, Parkville, Victoria, Australia
  12. Department of Microbiology & Immunology, The University of Melbourne, Parkville, Victoria, Australia
  13. Department of General Medicine, The Royal Children's Hospital, Parkville, Victoria, Australia
  14. School of Medicine, Deakin University, Geelong, Victoria, Australia
  15. Child health research unit, Barwon Health, Geelong, Victoria, Australia
  16. Neonatal Intensive Care Unit, Mercy Hospital for Women, Heidelberg, Victoria, Australia

Objectives: In addition to protecting against mycobacterial infections, Bacille Calmette-Guérin (BCG) vaccination has immunomodulatory effects which might result in off-target protection against unrelated respiratory tract infections other than tuberculosis. This is supported by in vitro data showing that neonatal BCG vaccination alters in vitro cytokine responses to unrelated pathogens1,2. In the MIS BAIR trial3, we aimed to determine whether, in a low-mortality setting, neonatal BCG vaccination reduces lower respiratory tract infections (LRTI) in infants.

Methods: In this RCT (NCT01906853), episodes of LRTI were identified by symptoms reported in 3-monthly questionnaires over the first year of life. Data were analysed by intention-to-treat using binary regression.

Results: 1272 infants were randomised to receive BCG-Denmark (median 1.5 days of age; IQR 0.9 to 2.5) or no BCG. The proportion of participants with ≥1 episodes LRTI in the first year of life was 54.8% for BCG-vaccinated infants compared to 58.0% in the control group (risk difference -3.2%, 95% CI -9.0 to 2.6%). There was some evidence that BCG vaccination provided greater protection against respiratory tract infections that occurred before an infant’s first diphtheria-tetanus-acellular pertussis vaccination, although the trial was not sufficiently powered to investigate this. There was no interaction observed between the primary outcome and sex, maternal BCG or the other pre-specified effect modifiers.

Conclusions: There is insufficient evidence to recommend neonatal BCG vaccination for the prevention of LRTI in infants in high-income settings.

  1. Freyne B, et al. Neonatal BCG Vaccination Influences Cytokine Responses to Toll-like Receptor Ligands and Heterologous Antigens. J Infect Dis 2018; 217(11): 1798-808
  2. Freyne B, et al. Neonatal BCG Vaccination Reduces Interferon-γ Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial. J Infect Dis. 2020;221(12):1999-2009
  3. Messina NL, et al. Study protocol for the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR), a randomised controlled trial to determine the non-specific effects of neonatal BCG vaccination in a low-mortality setting. BMJ Open. 2019; 15;9(12):e032844.