Are acellular vaccines driving the rise of pertactin-deficient Bordetella pertussis

无细胞疫苗是否会导致缺乏百日咳博德特氏菌的增加

基本信息

  • 批准号:
    10364771
  • 负责人:
  • 金额:
    $ 18.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-03-04 至 2023-02-28
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Bordetella pertussis, the respiratory pathogen responsible for “whooping cough,” causes an estimated 24 million cases of vaccine-preventable illness per year, resulting in an excess of 200,000 deaths annually. Importantly, the incidence of whooping cough in nations with high vaccine coverage is on the rise and has been recognized by both the CDC and NIH as a priority (re)emerging infectious pathogen of high concern. The flawed immunity conferred by acellular pertussis vaccines has been highly implicated in the re-emergence of whooping cough. Although acellular vaccines are reasonably effective in preventing severe disease, resultant immunity quickly wanes, and does not effectively prevent asymptomatic colonization or transmission of B. pertussis from vaccinated hosts to susceptible newborns. Rather than killed or attenuated bacteria, these vaccines are composed of 3-5 immunogenic proteins, notably, pertactin, a bacterial autotransporter that is now disrupted or absent in 85% of circulating strains in the United States. Bacterial adaptation in response to vaccine-driven pressure is suspected to have selected for pertactin-deficient strains, which may enable the bacterium to evade host immunity directed against pertactin. The high prevalence of pertactin deficient strains in the United States is taken as confirmatory evidence, but there is little robust experimental evidence to support or refute this hypothesis. More importantly, without clear experimental evidence, there is no consensus on how to respond, leaving the CDC and NIH to launch workshops and panels to try to tackle and understand the problem and consider possible solutions. Excitingly, we have developed a novel mouse model of natural infection that allows us, for the first time, to directly address vaccine driven selection for the loss of vaccine antigens, and here present preliminary data measuring the reduction in colonization and bacterial shedding from the nares of pertactin-deficient Bordetella bronchiseptica, a close ancestral relative of B. pertussis that naturally infects mice. Application of this model in vaccinated mice has generated preliminary data indicating that pertactin-deficient strains have an advantage in colonization and shedding from vaccinated hosts in comparison with wildtype B. bronchiseptica. These data are consistent with the expectation that pertactin deficiency measurably reduces fitness in unvaccinated hosts but increases fitness in vaccinated hosts. Therefore, we intend to employ our innovative mouse model to thoroughly investigate the role and effect of pertactin deficiency using representative isogenic B. pertussis strains. Together these experiments will provide the first direct evidence to either support or refute the controversial explanation of vaccine-driven evolution of B. pertussis, and thereby inform very different responses to the observed rise in incidence of disease and prevalence of circulating pertactin-deficient strains in countries with wide vaccine coverage.
项目总结

项目成果

期刊论文数量(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice.
  • DOI:
    10.3201/eid2708.203566
  • 发表时间:
    2021-08
  • 期刊:
  • 影响因子:
    11.8
  • 作者:
    Soumana IH;Linz B;Dewan KK;Sarr D;Gestal MC;Howard LK;Caulfield AD;Rada B;Harvill ET
  • 通讯作者:
    Harvill ET
Probing Immune-Mediated Clearance of Acute Middle Ear Infection in Mice.
The Neonatal Immune System and Respiratory Pathogens.
  • DOI:
    10.3390/microorganisms11061597
  • 发表时间:
    2023-06-16
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
    Sedney CJ;Harvill ET
  • 通讯作者:
    Harvill ET
Modeling the catarrhal stage of Bordetella pertussis upper respiratory tract infections in mice.
模拟小鼠百日咳博德特氏菌上呼吸道感染的卡他期。
  • DOI:
    10.1242/dmm.049266
  • 发表时间:
    2022-05-01
  • 期刊:
  • 影响因子:
    4.3
  • 作者:
    Soumana IH;Dewan KK;Linz B;Rivera I;Ma L;Howard LK;Caulfield AD;Sedney CJ;Blas-Machado U;Sebo P;Harvill ET
  • 通讯作者:
    Harvill ET
Evolution and Conservation of Bordetella Intracellular Survival in Eukaryotic Host Cells.
  • DOI:
    10.3389/fmicb.2020.557819
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    Rivera I;Linz B;Harvill ET
  • 通讯作者:
    Harvill ET
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Eric T Harvill其他文献

Eric T Harvill的其他文献

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{{ truncateString('Eric T Harvill', 18)}}的其他基金

An air-liquid interface system to study Bordetella pertussis interactions with respiratory epithelia
研究百日咳博德特氏菌与呼吸道上皮细胞相互作用的气液界面系统
  • 批准号:
    10665943
  • 财政年份:
    2023
  • 资助金额:
    $ 18.88万
  • 项目类别:
Protection against Bordetella pertussis transmission conferred by established and novel vaccines
现有疫苗和新型疫苗可预防百日咳博德特氏菌传播
  • 批准号:
    10375566
  • 财政年份:
    2021
  • 资助金额:
    $ 18.88万
  • 项目类别:
Protection against Bordetella pertussis transmission conferred by established and novel vaccines
现有疫苗和新型疫苗可预防百日咳博德特氏菌传播
  • 批准号:
    10194677
  • 财政年份:
    2021
  • 资助金额:
    $ 18.88万
  • 项目类别:
12th International Symposium on Bordetella
第12届博德特氏菌国际研讨会
  • 批准号:
    9761709
  • 财政年份:
    2019
  • 资助金额:
    $ 18.88万
  • 项目类别:
12th International Bordetella Symposium
第十二届国际博德特氏菌研讨会
  • 批准号:
    9805872
  • 财政年份:
    2018
  • 资助金额:
    $ 18.88万
  • 项目类别:
In vivo vaccine-driven evolution in Bordetella pertussis
百日咳博德特氏菌体内疫苗驱动的进化
  • 批准号:
    8986495
  • 财政年份:
    2015
  • 资助金额:
    $ 18.88万
  • 项目类别:
Systematic evaluation of B. pertussis ACT’s role as a protective antigen
百日咳博德特氏菌 ACT 作为保护性抗原的作用的系统评估
  • 批准号:
    9056231
  • 财政年份:
    2015
  • 资助金额:
    $ 18.88万
  • 项目类别:
The Microbiota Pathogen Competition
微生物群病原体竞赛
  • 批准号:
    9291478
  • 财政年份:
    2015
  • 资助金额:
    $ 18.88万
  • 项目类别:
Bordetella sp. Versus Microbiota
博德特氏菌属
  • 批准号:
    8896095
  • 财政年份:
    2014
  • 资助金额:
    $ 18.88万
  • 项目类别:
Evolution of the Bordetellae from Commensals to Pathogens
博德特氏菌从共生菌到病原体的进化
  • 批准号:
    7886472
  • 财政年份:
    2009
  • 资助金额:
    $ 18.88万
  • 项目类别:

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