Khandaker Shadia, Sharma Shilpee, Hall Tom, Lim Suzanna, Lehtonen Janne, Leung Stephanie, Ahmed Zabed Bin, Gorringe Andrew, Saha Samir K, Marchant Arnaud, Le Doare Kirsty, Kadioglu Aras, French Neil
Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, United Kingdom.
European Plotkin Institute for Vaccinology, ULB Centre for Research in Immunology, Université libre de Bruxelles, Brussels, Belgium.
J Infect Dis. 2025 Feb 20;231(2):e456-e467. doi: 10.1093/infdis/jiae607.
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.
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.
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.
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.
不同地理区域的B族链球菌(GBS)定植率和新生儿疾病发生率存在显著差异。例如,与英国和马拉维相比,孟加拉国报告的发病率明显较低。本研究调查了这种流行病学差异是否与这些地区对GBS的免疫反应相关。
对来自英国、孟加拉国和马拉维育龄妇女的血清样本进行了针对GBS荚膜多糖和Alp蛋白家族的天然获得性免疫球蛋白G(IgG)抗体的定性和定量分析。使用人源化小鼠模型评估了这些抗体清除阴道定植或保护新生儿免受GBS感染的功效。
孟加拉国妇女的血清型分布多样性最高,血清中针对GBS荚膜多糖Ia、Ib、II、III、IV和V以及Alp家族蛋白的IgG水平升高。相比之下,马拉维血清显示出最弱的抗体反应。在针对荚膜多糖Ib进行测试时,孟加拉国血清还显示出更高的IgG介导的补体沉积、调理吞噬杀伤和新生儿Fc受体结合。在人源化新生儿Fc受体小鼠模型中,孟加拉国血清导致GBS强毒株血清型Ib阴道定植的清除速度更快。此外,用孟加拉国血清进行被动免疫的母鼠所产后代的存活率显著提高。
本研究表明不同地理区域对GBS的免疫反应存在显著差异。这些发现强调了了解不同人群中GBS诱导的免疫反应的重要性,这可能会显著影响这些地区的疫苗效力。