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百日咳疫苗接种孕妇所生婴儿对博德特氏菌固有免疫反应的改变。

Modification of innate immune responses to Bordetella pertussis in babies from pertussis vaccinated pregnancies.

机构信息

Department of Metabolism, Development and Reproduction (MDR), Lecturer in Maternal and Fetal Health, Imperial College London, Institute of Reproductive and Developmental Biology (IRDB), Hammersmith Campus, London W12 0HS, UK; Section of Paediatrics, Department of Medicine, Imperial College London, UK.

Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.

出版信息

EBioMedicine. 2021 Oct;72:103612. doi: 10.1016/j.ebiom.2021.103612. Epub 2021 Oct 11.

Abstract

BACKGROUND

Tetanus, diphtheria, acellular pertussis, inactivated polio (Tdap-IPV) vaccines administered during pregnancy protect young infants from Bordetella pertussis (B. pertussis) infection. Whilst the impact of maternal Tdap-IPV vaccination on infants' humoral response to subsequent pertussis immunisation has been investigated, little is known about any impact on innate responses.

METHODS

We investigated the immune response to B. pertussis in mothers and infants from Tdap-IPV-vaccinated and unvaccinated pregnancies, utilising a whole blood assay and flow cytometric phenotyping of neonatal natural killer (NK) cells, monocytes and dendritic cells. Blood was collected from mother and umbilical cord at birth, and from infants at seven weeks (one week pre-primary pertussis immunisation) and five months of age (one month post-primary pertussis immunisation). 21 mothers and 67 infants were studied.

FINDINGS

Vaccinated women had elevated pro-inflammatory cytokine responses to B. pertussis. At birth, babies of vaccinated women had elevated IL-2 and IL-12 responses, elevated classical monocyte proportions, and reduced monocyte and NK cell cytokine responses. The elevated IL-2 response persisted to seven weeks-of-age, when lower IL-10 and IL-13 responses were also seen. One-month post-primary pertussis vaccination, infants from vaccinated pregnancies still had lower IL-10 responses to B. pertussis, as well as lower IL-4.

INTERPRETATION

This study suggests that pertussis vaccination during pregnancy impacts infant cellular immune responses, potentially contributing to the modification of antibody responses already reported following primary immunisation against B. pertussis.

FUNDING

National Institute for Health Research Imperial Biomedical Research Centre and IMmunising PRegnant women and INfants neTwork (funded by the GCRF Networks in Vaccines R&D).

摘要

背景

孕期接种破伤风、白喉、无细胞百日咳、灭活脊髓灰质炎(Tdap-IPV)疫苗可保护婴幼儿免受百日咳鲍特菌(B. pertussis)感染。虽然已经研究了母体 Tdap-IPV 疫苗接种对婴儿随后百日咳免疫接种的体液反应的影响,但对先天反应的影响知之甚少。

方法

我们利用全血检测和新生儿自然杀伤 (NK) 细胞、单核细胞和树突状细胞的流式细胞表型分析,研究了 Tdap-IPV 疫苗接种和未接种妊娠的母亲和婴儿对 B. pertussis 的免疫反应。在出生时从母亲和脐带中采集血液,并在 7 周(一次预 Primary 百日咳免疫接种前)和 5 个月(Primary 百日咳免疫接种后一个月)时从婴儿中采集血液。共研究了 21 名母亲和 67 名婴儿。

结果

接种疫苗的女性对 B. pertussis 的促炎细胞因子反应升高。出生时,接种疫苗女性的婴儿的 IL-2 和 IL-12 反应升高,经典单核细胞比例升高,单核细胞和 NK 细胞细胞因子反应降低。这种升高的 IL-2 反应持续到 7 周龄,此时也观察到较低的 IL-10 和 IL-13 反应。Primary 百日咳免疫接种后一个月,接种疫苗妊娠的婴儿对 B. pertussis 的 IL-10 反应仍然较低,IL-4 也较低。

解释

这项研究表明,孕期接种百日咳疫苗会影响婴儿的细胞免疫反应,可能导致已经报道的 Primary 百日咳免疫接种后抗体反应发生改变。

资金

英国国家健康研究所帝国生物医学研究中心和免疫妊娠妇女和婴儿网络(由 GCRF 疫苗研发网络资助)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/199b/8517834/06dc7d45922c/gr1.jpg

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