Shadia Khandaker

Background: Significant disparities in group B Streptococcus (GBS) colonization and neonatal disease rates have been documented across different geographic regions. For example, Bangladesh reports notably lower rates as compared with the United Kingdom and Malawi. This study investigates whether this epidemiologic 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 polysaccharide and the Alp protein family were conducted in serum samples from women of childbearing age in the United Kingdom, Bangladesh, and Malawi. The efficacy of these antibodies in clearing vaginal colonization or protecting newborns from GBS infection was assessed with humanized mouse models. Results: Bangladeshi women displayed the highest diversity in serotype distribution, with elevated IgG levels in the serum against GBS capsular polysaccharides 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 binding while tested against capsular polysaccharide Ib. In a humanized neonatal Fc receptor mouse model, Bangladeshi sera led to faster clearance of GBS virulent serotype Ib vaginal colonization. Additionally, offspring from dams passively immunized with Bangladeshi sera demonstrated notably increased survival rates. Conclusions: This study demonstrates significant variability in the immune response to GBS across different geographic regions. These findings underscore the importance of understanding GBS-induced immune response in diverse populations, which may significantly affect vaccine efficacy in these regions.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.