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

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

Author information

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: nigel.curtis@rch.org.au.

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

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