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Diversity in Naturally Acquired Immunity to Group B Streptococcus: A Comparative Study of Women from Bangladesh, Malawi, and the United Kingdom
The Journal of Infectious Diseases ( IF 5.0 ) Pub Date : 2024-12-18 , DOI: 10.1093/infdis/jiae607
Shadia Khandaker, Shilpee Sharma, Tom Hall, Suzanna Lim, Janne Lehtonen, Stephanie Leung, Zabed Bin Ahmed, Andrew Gorringe, Samir K Saha, Arnaud Marchant, Kirsty Le Doare, Aras Kadioglu, Neil French

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.

中文翻译:


对 B 组链球菌的自然获得性免疫的多样性:孟加拉国、马拉维和英国女性的比较研究



背景 B 组链球菌 (GBS) 定植和新生儿疾病发病率在不同地理区域存在显著差异。例如,与英国 (UK) 和马拉维相比,孟加拉国报告的比率明显较低。本研究调查了这种流行病学变异性是否与这些地区对 GBS 的免疫反应相关。方法 对英国、孟加拉国和马拉维育龄妇女血清样本中天然获得的针对 GBS 荚膜多糖 (CPS) 和 Alp 蛋白家族的免疫球蛋白 G (IgG) 抗体进行定性和定量分析。使用人源化小鼠模型评估这些抗体在清除阴道定植或保护新生儿免受 GBS 感染方面的疗效。结果 孟加拉国女性的血清型分布多样性最高,血清中针对 GBS 荚膜多糖 (CPS) - Ia、Ib、II、III、IV 和 V 以及 Alp 家族蛋白的免疫球蛋白 G (IgG) 水平升高。相比之下,马拉维血清表现出最弱的抗体反应。孟加拉国血清在检测 CPS Ib 时还显示 IgG 介导的补体沉积、调理吞噬杀伤和新生儿 Fc 受体 (FcRn) 结合增加。在人源化 FcRn 小鼠模型中,孟加拉国血清导致 GBS 毒力血清型 Ib 阴道定植的更快清除。此外,使用孟加拉国血清被动免疫的母体的后代表现出存活率显着提高。结论 本研究证明了不同地理区域对 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,这可能会显着影响这些地区的疫苗功效。
更新日期:2024-12-18
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