Bacille calmette-guérin, diphtheria-tetanus, and measles vaccine responses of infants born to mothers with active tuberculosis disease

Abstract

Background: Babies born to mothers with active tuberculosis disease (ATB) are at risk of poor clinical outcomes such as low birth weight and perinatal mortality. However, little is known about the influence of maternal exposure to ATB on their vaccine responses during infancy. We hypothesised that these babies will have reduced responses to vaccines compared to babies born to mothers without ATB. The study aimed to determine immunoglobulin G (IgG) and TB-specific cytokine responses to the infant vaccines: BCG, diphtheria, tetanus, and measles in plasma samples. Materials and methods: A longitudinal case-control study of baby-cases (born to mothers with bacteriologically confirmed ATB) and baby-controls (born to mothers without ATB) was carried out between September 2021 and June 2022. Quantitative IgG-specific BCG, diphtheria, tetanus, and measles ELISA assays were performed on infant plasma harvested from heparinised venous blood collected on first encounter after birth (month 0), at 3, 6 and 9 months, following immunisation as per the Uganda routine immunisation schedule for children under 1 year. Luminex (5-plex) assays for TB-specific cytokines: IL-17/IL-17A, IFN-γ, TNF-α, IL-2 and GM-CSF were also performed on baby QuantiFERON (QFT) plasma. Data was expressed as medians and interquartile ranges. Prism v9.5.1 was used for statistical analysis, and P<0.05 was considered statistically significant after performing the Mann-Whitney U-test. Results: ATB exposed infants had reduced BCG specific IgG at 6 months, diphtheria specific IgG at 6 months, and tetanus specific IgG at 0 and 3 months, vaccine responses in addition to increased IL-17/IL-17A cytokine responses compared to healthy controls in the TB2 tube. BCG cases/controls: [median (IQR): 122.1(97.28-136.8) versus 142.5(131.2-144.8), p=0.02]. Diphtheria cases/controls: [median (IQR): 0.006(0.0015-0.009) versus 0.011(0.006-0.1300), p=0.05]. Tetanus specific IgG at 6 months cases/controls: [median (IQR): 1.772(1.435-1.925) versus 2.583(2.322-2.955), p<0.0001]. IL-17/17A cases/controls: [median (IQR): 51.89(37.43-107.8) versus 42.10(30.44-65.49), p=0.01]. Conclusion: The findings demonstrate that babies born to mothers with active TB disease had lower BCG and Diphtheria (at 6 months)-Tetanus (0 & 3 months) IgG responses in addition to increased IL-17A combined CD4 & CD8 cytokine responses. These infants may require booster doses to benefit from vaccines.