Invasive Group B Streptococcus disease in young infants: understanding host and pathogen immunity ito inform maternal GBS vaccination development

小婴儿的侵袭性 B 族链球菌病：了解宿主和病原体免疫，为孕产妇 GBS 疫苗接种的开发提供信息

• 批准号: MR/S016570/1
• 负责人: Kirsty Le Doare
• 金额: $ 154.14万
• 依托单位: St George's, University of London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS016570%2F1
• 关键词: Invasive; Group; Streptococcus; disease; young

Infections during the first month of life are the leading cause of death in Africa and Group B Streptococcus (GBS) is emerging as a major culprit. GBS is a bacterium living in the back passage and vagina of women. GBS can cause lethal infection in pregnant women, stillbirths and premature births. It can be passed from mother to baby at birth or in breastmilk. Once passed on, GBS either remains harmless or causes severe pneumonia, sepsis and meningitis in new born babies. One way a mother protects her baby is by passing antibody against GBS through the placenta and in breastmilk after birth. However, we do not yet know how much antibody needs to be passed in this way to protect babies from disease. It is also unclear what changes GBS undergoes to become a potentially fatal bacteria.At present, babies in the Africa are still dying or being born too early and too small because of infections like GBS. Our research group is dedicated to finding out why GBS passes from mother to child, what the "protective" antibody levels need to be passed through the placenta to stop babies from getting sick in the first place and how to prevent GBS disease through new treatments such as maternal vaccination. We use a variety of different ways to find out the answers - through doing fieldwork (where mother and their babies are followed up over three months from birth to see what effect GBS has on their health) or by developing laboratory tests to see how antibody works to protect against GBS.We will use these answers to change how we look after pregnant women and monitor their babies for signs of infection. We do this so that we can improve the health of women and their babies. We bring together a number of different ways of working with the single aim of preventing GBS infections in babies (and their mothers). Our planned work includes the following:1. Following mothers and babies in Uganda and collecting blood samples to work out how much antibody a mother needs to pass to her infant to protect against GBS infection;2. Collecting bacteria and blood samples from babies who get GBS disease (via public health agencies we work with already) in the UK, Netherlands and France to compare if the type of bacteria found in different populations affects the amount of antibody needed to protect babies against GBS disease. 3. Helping hospitals in Uganda to investigate infections in babies by strengthening diagnostic laboratory capacity and working with clinicians to investigate and treat infections early. 4. Engaging with women in the African sites to understand whether a vaccine given to pregnant women to prevent GBS-as is currently being developed- is likely to be taken up sufficiently to be effective.

在非洲，出生第一个月期间的感染是主要的死亡原因，而B组链球菌(GBS)正在成为主要罪魁祸首。GBS是一种生活在女性后道和阴道内的细菌。GBS可导致孕妇、死产和早产的致命感染。它可以在出生时从母亲传给婴儿，也可以通过母乳传播。一旦传播，GBS要么是无害的，要么会引起新生儿的严重肺炎、败血症和脑膜炎。母亲保护婴儿的一种方法是在婴儿出生后通过胎盘和母乳传递抗GBS的抗体。然而，我们还不知道需要通过这种方式传递多少抗体来保护婴儿免受疾病的侵袭。目前还不清楚GBS经历了什么变化才成为一种潜在的致命细菌。目前，非洲的婴儿仍在死亡或过早出生，因为像GBS这样的感染。我们的研究小组致力于找出GBS为什么会从母亲传给孩子，需要通过胎盘传递什么样的保护性抗体水平才能从一开始就防止婴儿生病，以及如何通过母亲接种等新疗法来预防GBS疾病。我们使用各种不同的方法来寻找答案-通过田野调查(在出生后三个月内对母亲和她们的婴儿进行跟踪，以了解GBS对他们的健康有什么影响)，或者通过开发实验室测试，看看抗体如何作用于防止GBS。我们将利用这些答案来改变我们照顾孕妇的方式，并监测她们的婴儿是否有感染的迹象。我们这样做是为了改善妇女及其婴儿的健康。我们汇集了许多不同的工作方式，以实现预防婴儿(及其母亲)感染GBS的单一目标。我们计划的工作包括：1.跟踪乌干达的母亲和婴儿，收集血液样本，计算出母亲需要向婴儿传递多少抗体才能预防GBS感染；2.在英国、荷兰和法国(通过我们已经合作的公共卫生机构)收集患有GBS疾病的婴儿的细菌和血液样本，以比较在不同人群中发现的细菌类型是否会影响保护婴儿免受GBS疾病感染所需的抗体数量。3.通过加强诊断实验室能力和与临床医生合作，及早调查和治疗感染，帮助乌干达的医院调查婴儿感染情况。4.与非洲地区的妇女接触，了解目前正在开发的为预防GBS而向孕妇提供的疫苗是否有可能得到充分利用，从而发挥作用。

项目成果

Systematic review of Group B Streptococcal capsular types, sequence types and surface proteins as potential vaccine candidates.

B组链球菌囊类型，序列类型和表面蛋白作为潜在疫苗候选物的系统评价。

• DOI: 10.1016/j.vaccine.2020.08.052
• 发表时间: 2020-10-07
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Bianchi-Jassir F;Paul P;To KN;Carreras-Abad C;Seale AC;Jauneikaite E;Madhi SA;Russell NJ;Hall J;Madrid L;Bassat Q;Kwatra G;Le Doare K;Lawn JE
• 通讯作者: Lawn JE

Reliability of dried blood spot (DBS) cards in antibody measurement: A systematic review.

• DOI: 10.1371/journal.pone.0248218
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Amini F;Auma E;Hsia Y;Bilton S;Hall T;Ramkhelawon L;Heath PT;Le Doare K
• 通讯作者: Le Doare K