• 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, and MIS BAIR group.
• 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.
• Vaccine. 2019 Jun 19; 37 (28): 3735-3744.

IntroductionBacillus 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.MethodsAntibodies 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.ResultsAt 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.ConclusionThe 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.Copyright © 2019 Elsevier Ltd. All rights reserved.

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