The influence of neonatal Bacille Calmette-Guérin (BCG) immunisation on heterologous vaccine responses in infants

Petra Zimmermann; Susan Donath; Kirsten P Perrett; Nicole L Messina; Nicole Ritz; Mihai G Netea; Katie L Flanagan; Fiona R M van der Klis; Nigel Curtis; MIS BAIR group

doi:10.1016/j.vaccine.2019.03.016

The influence of neonatal Bacille Calmette-Guérin (BCG) immunisation on heterologous vaccine responses in infants

Vaccine. 2019 Jun 19;37(28):3735-3744. doi: 10.1016/j.vaccine.2019.03.016. Epub 2019 May 29.

Authors

Petra Zimmermann¹, Susan Donath², Kirsten P Perrett³, Nicole L Messina⁴, Nicole Ritz⁵, Mihai G Netea⁶, Katie L Flanagan⁷, Fiona R M van der Klis⁸, Nigel Curtis⁹; MIS BAIR group

Affiliations

¹ Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia; Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, Australia; Department of Pediatrics, Fribourg Hospital HFR and Faculty of Science and Medicine, University of Fribourg, Switzerland.
² Department of Paediatrics, The University of Melbourne, Parkville, Australia; Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Australia.
³ Food Allergy Research Group and Melbourne Children's Trial Centre, Murdoch Children's Research Institute, Melbourne, Australia; Departments of Allergy and Immunology and General Medicine, Royal Children's Hospital, Melbourne, Australia; School of Population and Global Health, The University of Melbourne, Parkville, Australia.
⁴ Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia.
⁵ Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, University of Basel Children's Hospital, Basel, Switzerland.
⁶ Department of Internal Medicine, Radboud Institute for Molecular Life Sciences and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, the Netherlands.
⁷ University of Tasmania, Launceston and Monash University, Clayton, Australia.
⁸ National Institute of Public Health and the Environment, Centre for Infectious Diseases, Bilthoven, the Netherlands.
⁹ Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia; Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, Australia. Electronic address: [email protected].

PMID: 31153688
DOI: 10.1016/j.vaccine.2019.03.016

Abstract

Introduction: Bacillus Calmette-Guérin vaccine (BCG), one of the most widely used vaccines, does not only provide protection against tuberculosis and other mycobacterial infections, but also has non-specific (heterologous) immunomodulatory effects. In participants in a randomised trial, we investigated the effect of neonatal BCG immunisation on antibody responses to routine infant vaccines given in the first year of life.

Methods: Antibodies against antigens in the diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), and the 13-valent pneumococcal conjugate vaccines were measured in 91 (45 BCG-vaccinated, 46 BCG-naïve) infants one month after, and in 310 (169 BCG-vaccinated, 141 BCG-naïve) infants seven months after immunisation at 6 weeks, 4 and 6 months of age. In addition, antibodies against meningococcus C, Hib, measles, mumps, and rubella were measured in 147 (78 BCG-vaccinated, 69 BCG-naïve) infants one month after immunisation at 12 months of age. The seroprotection rates for each vaccine and the geometric mean concentrations (GMC) of antibodies were compared in BCG-vaccinated and BCG-naïve infants.

Results: At 7 months of age, seroprotection rates were high in both BCG-vaccinated and BCG-naïve infants. At 13 months of age, seroprotection rates were lower than at 7 months of age, particularly for pertussis and a number of pneumococcal antigens, with generally higher rates for the latter in BCG-vaccinated infants. Although not statistically significant, antibody responses in BCG-vaccinated infants were consistently higher against diphtheria, tetanus, and pneumococcal antigens at both 7 and 13 months of age, and against measles and mumps at 13 months of age, but were lower against Hib one month after immunisation at both 7 and 13 months of age.

Conclusion: The immunomodulatory effect of BCG on antibody responses to heterologous vaccines adds to the evidence that BCG immunisation at birth has broad heterologous effects on the infant immune system.

Keywords: Antibodies; Humoral; Immunoglobulin; Non-specific; Seroprotection; Titre; Vaccination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Bacterial / immunology
Antibody Formation / immunology*
BCG Vaccine / immunology*
Diphtheria / immunology
Diphtheria-Tetanus-Pertussis Vaccine / immunology
Female
Haemophilus Vaccines / immunology
Haemophilus influenzae type b / immunology
Humans
Immunization / methods
Infant
Male
Measles / immunology
Pneumococcal Vaccines / immunology
Poliovirus Vaccine, Inactivated / immunology
Tetanus / immunology
Vaccination / methods
Vaccines, Conjugate / immunology*
Whooping Cough / immunology

Substances

13-valent pneumococcal vaccine
Antibodies, Bacterial
BCG Vaccine
Diphtheria-Tetanus-Pertussis Vaccine
Haemophilus Vaccines
Pneumococcal Vaccines
Poliovirus Vaccine, Inactivated
Vaccines, Conjugate