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. © 2019 Elsevier Ltd
