Influenza during pregnancy: The emergence of highly virulent H1N1 influenza virus strains and consequences for maternal and offspring’s health
怀孕期间流感:高毒力 H1N1 流感病毒株的出现及其对孕产妇和后代健康的影响
基本信息
- 批准号:269120464
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Clinical Research Units
- 财政年份:2015
- 资助国家:德国
- 起止时间:2014-12-31 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Compared to the general population, pregnant women are more likely to suffer from severe and even fatal influenza. During the 2009 H1N1 influenza pandemic, high morbidity and mortality rates were repeatedly observed among pregnant women. We have previously established an influenza virus infection model in pregnant mice, which reproduces the clinical features observed in pregnant women with severe courses of disease. Insights arising from this mouse model obtained during the first funding period of the KFO296 revealed that the anti-viral immune response in the pregnant mouse was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8+ T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. Thus, in continuation of this project, we now seek to pursue a translational approach, in which we will characterise influenza virus isolates from pregnant women for the presence of innate immune escape variants with increased pathogenicity. Interestingly, our application of the steroid hormone progesterone in order to mirror a pregnancy-like endocrine milieu in non-pregnant mice, revealed an increased mortality, suggesting that progesterone is involved in dampening the host’s immune response against pandemic H1N1 virus. Thus, another focus will be to understand how progesterone may affect the anti-viral innate and adaptive immune response. Moreover, we will analyse maternal microchimerism as a potential factor to modulate offspring’s health towards influenza virus infections in the long-term. In summary, our project will elucidate underlying mechanisms that mediate severe influenza in pregnant women and potentially affect offspring’s immune response. Results obtained from this proposal will underscore the importance of the currently poor vaccination compliance in pregnant women and might further open novel therapeutic avenues.
与普通人群相比,孕妇更容易患上严重甚至致命的流感。在2009年H1N1流感大流行期间,孕妇的发病率和死亡率居高不下。我们之前已经在怀孕小鼠中建立了流感病毒感染模型,该模型再现了在病程严重的孕妇中观察到的临床特征。在KFO296的第一个资助期内从这个小鼠模型中获得的见解表明,与未怀孕的宿主相比,怀孕小鼠的抗病毒免疫反应受到了显著的限制。这包括I型干扰素反应降低以及CD8+T细胞向肺内迁移受损。多方面未能在同种异体妊娠小鼠中启动抗病毒反应,导致了一个不那么严格的选择环境,促进了2009年H1N1病毒变种的出现,这些变种特异性地中和了I型干扰素反应,并介导了病毒致病性的增加。因此,在这个项目的继续中,我们现在寻求一种翻译的方法,在这种方法中,我们将表征孕妇的流感病毒分离株是否存在具有更高致病性的先天性免疫逃逸变异。有趣的是,我们应用类固醇激素黄体酮来反映非怀孕小鼠的妊娠样内分泌环境,发现死亡率增加,这表明黄体酮参与抑制宿主对大流行H1N1病毒的免疫反应。因此,另一个重点将是了解黄体酮如何影响抗病毒的先天免疫反应和获得性免疫反应。此外,我们将分析母体微嵌合体作为一个潜在因素来长期调节后代的健康以应对流感病毒感染。总而言之,我们的项目将阐明导致孕妇患严重流感并可能影响后代免疫反应的潜在机制。从这项提议中获得的结果将强调目前孕妇接种疫苗依从性差的重要性,并可能进一步开辟新的治疗途径。
项目成果
期刊论文数量(0)
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Professorin Dr. Petra Clara Arck其他文献
Professorin Dr. Petra Clara Arck的其他文献
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{{ truncateString('Professorin Dr. Petra Clara Arck', 18)}}的其他基金
Towards improving pregnancy success rates: Understanding the functional role and memory development of CD4+ regulatory T cell subsets during first and second pregnancies.
提高妊娠成功率:了解 CD4 调节性 T 细胞亚群在第一次和第二次妊娠期间的功能作用和记忆发育。
- 批准号:
315517090 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Research Grants
Prenatal stress challenge in mice: the role of vertically transmitted maternal glucocorticoids and immune cells in modulating offspring‘s immunity
小鼠产前应激挑战:垂直传播的母体糖皮质激素和免疫细胞在调节后代免疫力中的作用
- 批准号:
269321214 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Clinical Research Units
Fetale Ursache immunologischer Erkrankungen: Einfluss von mütterlichem Mikrochimärismus während der Schwangerschaft und dessen Modulation durch Stressbelastung
免疫疾病的胎儿原因:妊娠期间母体微嵌合的影响及其应激调节
- 批准号:
192644356 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Research Grants
Immune mediated depressive behaviour: causes, consequences and therapeutic opportunities
免疫介导的抑郁行为:原因、后果和治疗机会
- 批准号:
28996577 - 财政年份:2007
- 资助金额:
-- - 项目类别:
Research Grants
Haarwuchsstörungen durch Stress: Nachweis, pathophysiologische Grundlagen und neuropharmakologische Manipulation, GEM mit PA 345/11-2
压力引起的毛发生长障碍:证据、病理生理学基础和神经药理学操作,GEM with PA 345/11-2
- 批准号:
5374272 - 财政年份:2002
- 资助金额:
-- - 项目类别:
Research Grants
Long-term programming of sex differences in immunity by prenatal exposure to stress
通过产前暴露于压力对免疫性别差异进行长期规划
- 批准号:
453860814 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Units
相似海外基金
Pandemic A/H1N1 Influenza Vaccination or Infection During Pregnancy and Offspring Autoimmune Outcomes.
流行性 A/H1N1 流感疫苗接种或怀孕期间感染和后代自身免疫结果。
- 批准号:
486363 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Studentship Programs
Understanding the Impact of Influenza A Virus Infection During Pregnancy
了解甲型流感病毒感染对怀孕期间的影响
- 批准号:
10390105 - 财政年份:2022
- 资助金额:
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Control of influenza virus induced type I interferon signaling during pregnancy
妊娠期间流感病毒诱导的 I 型干扰素信号传导的控制
- 批准号:
10584008 - 财政年份:2022
- 资助金额:
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Understanding the Impact of Influenza A Virus Infection During Pregnancy
了解甲型流感病毒感染对怀孕期间的影响
- 批准号:
10673592 - 财政年份:2022
- 资助金额:
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INFLUENZA-SPECIFIC IMMUNITY AND RESPONSES TO INACTIVATED INFLUENZA VACCINE IN INFANTS: EFFECT OF MATERNAL VACCINATION DURING PREGNANCY
婴儿流感特异性免疫力和对灭活流感疫苗的反应:怀孕期间母亲接种疫苗的影响
- 批准号:
10426208 - 财政年份:2020
- 资助金额:
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INFLUENZA-SPECIFIC IMMUNITY AND RESPONSES TO INACTIVATED INFLUENZA VACCINE IN INFANTS: EFFECT OF MATERNAL VACCINATION DURING PREGNANCY
婴儿流感特异性免疫力和对灭活流感疫苗的反应:怀孕期间母亲接种疫苗的影响
- 批准号:
10197834 - 财政年份:2020
- 资助金额:
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INFLUENZA-SPECIFIC IMMUNITY AND RESPONSES TO INACTIVATED INFLUENZA VACCINE IN INFANTS: EFFECT OF MATERNAL VACCINATION DURING PREGNANCY
婴儿流感特异性免疫力和对灭活流感疫苗的反应:怀孕期间母亲接种疫苗的影响
- 批准号:
10065972 - 财政年份:2020
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Effect of Maternal Influenza Vaccination during Pregnancy on Risk of Infant Influenza
孕期母亲接种流感疫苗对婴儿流感风险的影响
- 批准号:
10394892 - 财政年份:2018
- 资助金额:
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Effect of Maternal Influenza Vaccination during Pregnancy on Risk of Infant Influenza
孕期母亲接种流感疫苗对婴儿流感风险的影响
- 批准号:
9913471 - 财政年份:2018
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Assessing the association between laboratory-confirmed seasonal influenza during pregnancy and health outcomes in early childhood
评估妊娠期间实验室确诊的季节性流感与幼儿期健康结果之间的关联
- 批准号:
411287 - 财政年份:2018
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Studentship Programs