Abstract

BACKGROUND: Significant disparities in Group B Streptococcus (GBS) colonisation and neonatal disease rates have been documented across different geographical regions. For example, Bangladesh reports notably lower rates compared to the United Kingdom (UK) and Malawi. This study investigates whether this epidemiological variability correlates with the immune response to GBS in these regions. METHODS: Qualitative and quantitative analyses of naturally acquired immunoglobulin G (IgG) antibodies against GBS capsular polysaccharides (CPS) and the Alp protein family were conducted in serum samples from women of childbearing age in the UK, Bangladesh, and Malawi. The efficacy of these antibodies in clearing vaginal colonisation or protecting newborns from GBS infection was assessed using humanised mouse models. RESULTS: Bangladeshi women displayed the highest diversity in serotype distribution, with elevated immunoglobulin G (IgG) levels in the serum against GBS capsular polysaccharides (CPS)- Ia, Ib, II, III, IV, and V, as well as Alp family proteins. In contrast, Malawian sera demonstrated the weakest antibody response. Bangladeshi sera also showed heightened IgG-mediated complement deposition, opsonophagocytic killing and neonatal Fc receptor (FcRn)-binding while tested against CPS Ib. In a humanised FcRn mouse model, Bangladeshi sera led to faster clearance of GBS virulent serotype Ib vaginal colonisation. Additionally, offspring from dams passively immunised with Bangladeshi sera demonstrated notably increased survival rates. CONCLUSIONS: This study demonstrates significant variability in the immune response to GBS across different geographical regions. These findings underscore the importance of understanding GBS-induced immune response in diverse populations, which may significantly impact vaccine efficacy in these regions.