The impact of maternal infection with Mycobacterium tuberculosis on the infant response to BCG immunisation

母亲结核分枝杆菌感染对婴儿卡介苗免疫反应的影响

• 批准号: MR/K019708/1
• 负责人: Alison Elliott
• 金额: $ 128.28万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK019708%2F1
• 关键词: impact; maternal; infection; Mycobacterium; tuberculosis

Tuberculosis (TB) is still a very important health problem in sub-Saharan Africa. Many people are infected with Mycobacterium tuberculosis (M.tb) (the bacterium that causes tuberculosis) in these countries, but the infection is kept in check by the immune system and the people remain healthy. We call this latent infection. Usually, only about 10% of infected individuals will progress to having the active form of the disease in their lifetime. However, when people do get the active disease, they can infect many other people, and so the cycle continues. TB kills approximately 2 million people every year, and another 10 million people become infected with M.tb every year. One way to eradicate TB would be to immunise everyone with an effective vaccine. Unfortunately, to date there is only one licensed vaccine, BCG, which was first introduced almost 100 years ago. BCG is given in many countries at, or around the time of birth. In sub-Saharan Africa, this immunisation schedule has been very effective at preventing some of the more severe (and deadly) forms of the disease in children, but the vaccine does not protect against the more common, active pulmonary form of the disease (the disease affecting the lungs) that occurs in adolescents and adults. By contrast, in countries such as the UK, BCG immunisation gives up to 80% protection against active pulmonary disease in adolescents and adults. We do not know why BCG should give poorer protection against pulmonary TB in sub-Saharan African countries compared to European countries, and our study is aimed at understanding this phenomenon.Since latent M.tb infection is more prevalent in sub-Saharan Africa than in the UK (for example), we think that part of the answer may lie in whether a mother has an underlying, latent M.tb infection. We think that this infection in a pregnant woman may affect the developing baby's own immune system. For example, if the baby is exposed to maternal M.tb infection while in the womb, when its immune system is developing, the immune system may regard the presence of Mtb infection as "normal" and fail to mount a suitable reaction to the infection. In such a case, when the baby is born and is given the BCG vaccine, the baby may not respond in the same way as a baby who was born of a mother without a latent M.tb infection (such as mothers in the UK).Our study will therefore look at the infant immune response to the BCG vaccine. We will examine immune responses in babies born in sub-Saharan Africa from mothers who do and don't have a latent M.tb infection, and we will compare their results with results from babies born of mothers in the UK, where M.tb infection is much less common. These results will give us a good idea of whether maternal M.tb infection status affects the infant response to BCG. If it does, then we may have to think about testing young women for the infection, and treating them before or during pregnancy.

在撒哈拉以南非洲，结核病仍然是一个非常重要的健康问题。在这些国家，许多人感染了结核分枝杆菌(M.tb)(导致结核病的细菌)，但免疫系统控制住了感染，人们保持健康。我们称之为潜伏感染。通常，只有大约10%的感染者会在他们的一生中发展为这种疾病的活动性形式。然而，当人们患上活动性疾病时，他们会感染许多其他人，因此循环仍在继续。结核病每年导致大约200万人死亡，每年还有1000万人感染结核分枝杆菌。根除结核病的一种方法是为每个人接种有效的疫苗。不幸的是，到目前为止，只有一种获得许可的疫苗，即近100年前首次引入的卡介苗。卡介苗在许多国家都是在出生时或出生前后接种的。在撒哈拉以南非洲，这一免疫计划在预防儿童中一些更严重(和致命)的疾病方面非常有效，但疫苗无法预防更常见、更活跃的肺部疾病(影响肺部的疾病)，这种疾病发生在青少年和成年人身上。相比之下，在英国等国家，在青少年和成年人中接种卡介苗可对活动性肺部疾病提供高达80%的保护。我们不知道为什么与欧洲国家相比，卡介苗对撒哈拉以南非洲国家的肺结核病提供的保护更差，我们的研究旨在了解这一现象。由于潜伏的结核分枝杆菌感染在撒哈拉以南非洲比英国更普遍(例如)，我们认为部分答案可能在于母亲是否有潜在的结核分枝杆菌感染。我们认为，孕妇的这种感染可能会影响发育中的婴儿自身的免疫系统。例如，如果婴儿在子宫中暴露于母体结核分枝杆菌感染，当其免疫系统正在发育时，免疫系统可能会认为存在结核分枝杆菌感染是“正常的”，无法对感染做出适当的反应。在这种情况下，当婴儿出生并接种卡介苗时，婴儿的反应可能不会像没有潜在结核分枝杆菌感染的母亲(如英国的母亲)所生的婴儿一样。因此，我们的研究将关注婴儿对卡介苗的免疫反应。我们将检查撒哈拉以南非洲出生的婴儿的免疫反应，这些婴儿的母亲是否有潜在的结核分枝杆菌感染，并将他们的结果与英国母亲出生的婴儿的结果进行比较，英国母亲出生的婴儿感染结核分枝杆菌的情况要少得多。这些结果将让我们很好地了解母体结核分枝杆菌感染状况是否会影响婴儿对卡介苗的反应。如果是这样，那么我们可能不得不考虑对年轻女性进行感染测试，并在怀孕前或怀孕期间对她们进行治疗。

项目成果

Establishing a single-sex controlled human Schistosoma mansoni infection model for Uganda: protocol for safety and dose-finding trial.

• DOI: 10.1093/immadv/ltad010
• 发表时间: 2023
• 期刊: Immunotherapy advances

Molecular characterization of the 2022 Sudan virus disease outbreak in Uganda.

• DOI: 10.1128/jvi.00590-23
• 发表时间: 2023-10-31
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Balinandi, Stephen;Whitmer, Shannon;Mulei, Sophia;Nassuna, Charity;Pimundu, Godfrey;Muyigi, Tonny;Kainulainen, Markus;Shedroff, Elizabeth;Krapiunaya, Inna;Scholte, Florine;Nyakarahuka, Luke;Tumusiime, Alex;Kyondo, Jackson;Baluku, Jimmy;Kiconco, Jocelyn;Harris, Julie R.;Ario, Alex R.;Kagirita, Atek;Bosa, Henry K.;Ssewanyana, Isaac;Nabadda, Susan;Mwebesa, Henry G.;Aceng, Jane R.;Atwine, Diana;Lutwama, Julius J.;Shoemaker, Trevor R.;Montgomery, Joel M.;Kaleebu, Pontiano;Klena, John D.
• 通讯作者: Klena, John D.

The Yin and Yang of the Non-Specific Effects of Vaccines.

• DOI: 10.1016/j.ebiom.2017.08.008
• 发表时间: 2017-09
• 期刊: EBioMedicine
• 影响因子: 11.1
• 作者: Cose S

Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants.

利用免疫遗传学针对孟加拉国婴儿的乙型肝炎疫苗逃逸。

• DOI: 10.1101/2023.06.26.23291885
• 发表时间: 2023
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Butler-Laporte,Guillaume;Auckland,Kathryn;Noor,Zannatun;Kabir,Mamun;Alam,Masud;Carstensen,Tommy;Wojcik,GenevieveL;Chong,AmandaY;Pomilla,Cristina;Noble,JanelleA;McDevitt,ShanaL;Smits,Gaby;Wareing,Susan;vanderKlis,FionaRm

Immunology in Africa.

• DOI: 10.1111/tmi.12599
• 发表时间: 2015-12
• 期刊: Tropical medicine & international health : TM & IH
• 作者: Cose S;Bagaya B;Nerima B;Joloba M;Kambugu A;Tweyongyere R;Dunne DW;Mbidde E;Kaleebu P;Elliott AM
• 通讯作者: Elliott AM