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.


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


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