Protective immunity induced by newborn BCG vaccination

新生儿接种卡介苗诱导的保护性免疫

• 批准号: 7596300
• 负责人: Willem Albert Hanekom
• 金额: $ 50.21万
• 依托单位: UNIVERSITY OF CAPE TOWN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-14 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596300
• 关键词: 5 year old; Address; Adult; African; Age; Antibody Formation; Biological Assay; Birth; Blood; Blood Volume; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Clinical; Complement; Complex; DNA; Disease; Exposure to; Genes; Genus Mycobacterium; Human; Humoral Immunities; Immune; Immune response; Immunity; Incidence; Infant; Knowledge; Licensing; Longitudinal Studies; Measures; Newborn Infant; Outcome; Play; Process; Pulmonary Tuberculosis; Rural; Site; South Africa; T-Lymphocyte; Testing; Tuberculosis; Tuberculosis Vaccines; Vaccinated; Vaccination; Vaccines; Whole Blood; case control; novel; response; vaccination against tuberculosis; vaccine evaluation

DESCRIPTION (provided by applicant): Our objective is a better understanding of vaccination-induced protection against tuberculosis (TB) in humans. This knowledge is critical for developing novel TB vaccines. Our first aim is to characterize T cell immunity following BCG vaccination of newborns. We will focus on longitudinal changes in specific CD4+ and CD8+ T cell immunity conventionally associated with protection against TB. We will test the hypothesis that regulatory CD4+ T cells are induced by BCG, and that these cells modulate specific immune outcome. Newly validated whole blood assays will be used to measure immunity in infants from South Africa, where vaccination with BCG at birth is routine, and where the TB incidence is very high. Complementary, longitudinal studies of adults vaccinated with BCG will also be performed, as larger blood volumes will allow a more comprehensive functional immune assessment. Our second aim is to identify immune components that are associated with BCG-induced protection against infant TB. To address this aim, we have already collected processed and stored blood from 5,675 10-week old South African infants, vaccinated with BCG at birth. We have subsequently identified >500 of these infants who have developed TB disease (cases), or who have remained healthy despite exposure to adults with TB (controls). We will retrieve stored blood of cases and controls, and compare conventional and regulatory immunity induced by BCG. Additionally, we hypothesize that we will identify novel genes involved in BCG-induced protection against TB, with DNA micro-array analysis. Our third aim is to determine whether the antibody response to BCG contributes to protection against TB. We will characterize this response in newborns vaccinated with BCG. We will compare the antibody response between BCG-vaccinated infants who are protected against TB, and those not protected.

描述（由申请人提供）：我们的目标是更好地理解人类疫苗接种诱导的针对结核病（TB）的保护。这种知识对于开发新型结核病疫苗至关重要。我们的第一个目的是表征新生儿BCG疫苗接种后T细胞免疫。我们将重点关注特定CD4+和CD8+ T细胞免疫的纵向变化，从传统上与针对TB的保护相关。我们将检验以下假设：调节性CD4+ T细胞由BCG诱导，并且这些细胞调节了特定的免疫结果。新验证的全血分析将用于测量来自南非的婴儿的免疫力，那里的BCG在出生时进行了疫苗接种，而在TB发病率很高。还将对接受BCG疫苗接种的成年人进行互补的纵向研究，因为较大的血量将允许更全面的功能免疫评估。我们的第二个目的是确定与BCG诱导的针对婴儿结核的保护的免疫成分。为了解决这一目标，我们已经收集了5,675个10周的南非婴儿的加工和储存的血液，出生时接受了BCG疫苗接种。随后，我们确定了患有结核病疾病（病例）或尽管暴露于结核病（对照组）的这些婴儿或仍然健康的婴儿。我们将检索病例和对照的储存的血液，并比较BCG诱导的常规和调节免疫。此外，我们假设我们将通过DNA微阵列分析来鉴定与BCG诱导的针对TB的保护有关的新基因。我们的第三个目的是确定对BCG的抗体反应是否有助于保护结核病。我们将在接种BCG接种的新生儿中表征这种反应。我们将比较受保护的BCG接种疫苗的婴儿与未受到保护的抗体反应。

项目成果

Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response.

• DOI: 10.1016/j.vaccine.2009.06.103
• 发表时间: 2009-09-04
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Kagina BM;Abel B;Bowmaker M;Scriba TJ;Gelderbloem S;Smit E;Erasmus M;Nene N;Walzl G;Black G;Hussey GD;Hesseling AC;Hanekom WA
• 通讯作者: Hanekom WA

Predominance of interleukin-22 over interleukin-17 at the site of disease in human tuberculosis.

• DOI: 10.1016/j.tube.2011.06.009
• 发表时间: 2011-11
• 期刊: Tuberculosis (Edinburgh, Scotland)
• 作者: Matthews K;Wilkinson KA;Kalsdorf B;Roberts T;Diacon A;Walzl G;Wolske J;Ntsekhe M;Syed F;Russell J;Mayosi BM;Dawson R;Dheda K;Wilkinson RJ;Hanekom WA;Scriba TJ
• 通讯作者: Scriba TJ

Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load.

• DOI: 10.4049/jimmunol.1101122
• 发表时间: 2011-09-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Day CL;Abrahams DA;Lerumo L;Janse van Rensburg E;Stone L;O'rie T;Pienaar B;de Kock M;Kaplan G;Mahomed H;Dheda K;Hanekom WA
• 通讯作者: Hanekom WA

Differential DNA methylation of potassium channel KCa3.1 and immune signalling pathways is associated with infant immune responses following BCG vaccination.

• DOI: 10.1038/s41598-018-31537-9
• 发表时间: 2018-08-30
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Hasso-Agopsowicz M;Scriba TJ;Hanekom WA;Dockrell HM;Smith SG
• 通讯作者: Smith SG

Novel application of Ki67 to quantify antigen-specific in vitro lymphoproliferation.

• DOI: 10.1016/j.jim.2010.08.007
• 发表时间: 2010-10-31
• 期刊: JOURNAL OF IMMUNOLOGICAL METHODS
• 影响因子: 2.2
• 作者: Soares, Andreia;Govender, Lerisa;Hughes, Jane;Mavakla, Wendy;de Kock, Marwou;Barnard, Charlene;Pienaar, Bernadette;van Rensburg, Esme Janse;Jacobs, Gail;Khomba, Gloria;Stone, Lynnette;Abel, Brian;Scriba, Thomas J.;Hanekom, Willem A.
• 通讯作者: Hanekom, Willem A.