Le Doare Kirsty, Faal Amadou, Jaiteh Mustapha, Sarfo Francess, Taylor Stephen, Warburton Fiona, Humphries Holly, Birt Jessica, Jarju Sheikh, Darboe Saffiatou, Clarke Edward, Antonio Martin, Foster-Nyarko Ebenezer, Heath Paul T, Gorringe Andrew, Kampmann Beate
Centre for International Child Health, Imperial College London, Norfolk Place, London W2 1PG, UK,; Paediatric Infectious Diseases Research Group, St. George's University of London, Cranmer Terrace, London SW17 0TE, UK; Vaccines & Immunity Theme, MRC Unit The Gambia, Atlantic Road, Fajara, Gambia.
Vaccines & Immunity Theme, MRC Unit The Gambia, Atlantic Road, Fajara, Gambia.
Vaccine. 2017 May 19;35(22):2970-2978. doi: 10.1016/j.vaccine.2017.04.013. Epub 2017 Apr 24.
Vertical transmission of Group B Streptococcus (GBS) is a prerequisite for early-onset disease and a consequence of maternal GBS colonization. Disease protection is associated with maternally-derived anti-GBS antibody. Using a novel antibody-mediated C3b/iC3b deposition flow cytometry assay which correlates with opsonic killing we developed a model to assess the impact of maternally-derived functional anti-GBS antibody on infant GBS colonization from birth to day 60-89 of life.
Rectovaginal swabs and cord blood (birth) and infant nasopharyngeal/rectal swabs (birth, day 6 and day 60-89) were obtained from 750 mother/infant pairs. Antibody-mediated C3b/iC3b deposition with cord and infant sera was measured by flow cytometry.
We established that as maternally-derived anti-GBS functional antibody increases, infant colonization decreases at birth and up to three months of life, the critical time window for the development of GBS disease. Further, we observed a serotype (ST)-dependent threshold above which no infant was colonized at birth. Functional antibody above the upper 95th confidence interval for the geometric mean concentration was associated with absence of infant GBS colonization at birth for STII (p<0.001), STIII (p=0.01) and STV (p<0.001). Increased functional antibody was also associated with clearance of GBS between birth and day 60-89.
Higher concentrations of maternally-derived antibody-mediated complement deposition are associated with a decreased risk of GBS colonization in infants up to day 60-89 of life. Our findings are of relevance to establish thresholds for protection following vaccination of pregnant women with future GBS vaccines.
B族链球菌(GBS)的垂直传播是早发型疾病的先决条件,也是母亲GBS定植的结果。疾病保护与母体来源的抗GBS抗体有关。我们使用一种新型的抗体介导的C3b/iC3b沉积流式细胞术检测方法(该方法与调理吞噬杀伤作用相关)建立了一个模型,以评估母体来源的功能性抗GBS抗体对婴儿从出生到生命第60 - 89天GBS定植的影响。
从750对母婴中获取直肠阴道拭子、脐带血(出生时)以及婴儿鼻咽/直肠拭子(出生时、第6天和第60 - 89天)。通过流式细胞术测量脐带血和婴儿血清中抗体介导的C3b/iC3b沉积。
我们确定,随着母体来源的抗GBS功能性抗体增加,婴儿在出生时以及生命的前三个月(GBS疾病发生的关键时间窗口)的定植率降低。此外,我们观察到一种血清型(ST)依赖性阈值,高于该阈值时没有婴儿在出生时被定植。对于STII(p<0.001)、STIII(p = 0.01)和STV(p<0.001),几何平均浓度高于第95百分位数置信区间上限的功能性抗体与出生时婴儿无GBS定植相关。功能性抗体增加也与出生至第60 - 89天GBS的清除有关。
在生命第60 - 89天之前,母体来源的抗体介导的补体沉积浓度较高与婴儿GBS定植风险降低相关。我们的研究结果对于确定未来用GBS疫苗为孕妇接种疫苗后的保护阈值具有重要意义。