Identifying the Most Effective Adjuvant(s) for Leading Group A Streptococcal Vaccine Antigens in Preclinical Mouse and Nonhuman Primate Models

在临床前小鼠和非人灵长类动物模型中确定 A 组链球菌疫苗抗原最有效的佐剂

基本信息

  • 批准号:
    10577066
  • 负责人:
  • 金额:
    $ 70.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-01-05 至 2027-12-31
  • 项目状态:
    未结题

项目摘要

SUMMARY The leading human bacterial pathogen group A Streptococcus (GAS) causes over 700,000,000 cases of superficial disease such as pharyngitis and pyoderma each year but can also lead to serious invasive infections and autoimmune sequelae, which combine to make GAS one of top 10 causes of infection-associated deaths worldwide. The highest mortality burden of GAS disease is caused by rheumatic heart disease (RHD), which results from repeated bouts of acute rheumatic fever (ARF). It is difficult to overstate the urgent public health need for a safe and efficacious GAS vaccine for human use. A significant number of experimental GAS vaccines are backlogged in preclinical development, with questions around safety, global GAS strain coverage, potential for efficacy in humans (i.e. lack of animal efficacy model data that accurately reflects disease). We have recently demonstrated that choice of adjuvant plays a pivotal role in imparting protective efficacy for an experimental multi-component GAS subunit vaccine in both a murine invasive disease model and the non-human primate (NHP) model that closely recapitulates GAS pharyngitis, the primary target for vaccine protection. Moreover, these studies suggest that promoting immunity skewed towards Th1 may elicits optimal protection beyond that afforded by the standard Alum adjuvant formulation. Herein, our highly experienced team of scientists with an extensive track record of productive collaboration will expand this important line of investigation to deliver proof- of-concept of the impact of adjuvant on the efficacy of three leading experimental GAS vaccines: (1) a 30-valent N-terminal M protein vaccine (StreptAnova) from the University of Tennessee that has reached phase 1 human trials; (2) Vaxcyte VAX-AI from Vaxcyte, Inc. in collaboration with UC San Diego, a conjugate vaccine with modified group A carbohydrate conjugate, and GAS proteins SLO, SpyAD, SCPA; and (3) Combo#5 from the University of Queensland incorporating 5 conserved immunogenic GAS antigens: SLO, SCPA, SpyCEP, ADI, TF. The vaccines will be formulated with Alum or selected emulsion and liposome-based adjuvants, using four distinct mouse models (skin, intranasal, intraperitoneal and invasive disease). Protective efficacy, immune response, correlates of protection, and vaccine safety (cross reactivity to human heart tissue) will be assessed. Finally, protection afforded by three selected vaccine-adjuvant combinations will be assessed in the non-human primate model of GAS pharyngitis, which most closely mimics GAS primary infection of humans, and clinical scoring and vaccine safety parameters determined. To advance the entire GAS vaccine field, our head-to-head comparison of M protein and non-M protein GAS vaccines, in both select mouse models and the NHP pharyngitis model, will have broad implications. across the field. We will identify the most efficacious antigen and adjuvant formulations using the animal models we have developed. Adjuvants that we identify will be available for use with other GAS vaccines via the Vaccine Formulation Institute (Switzerland), a not-for-profit organization who help guide advancement of effective formulations toward human trials and commercial use.
总结

项目成果

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会议论文数量(0)
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Victor Nizet其他文献

Victor Nizet的其他文献

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{{ truncateString('Victor Nizet', 18)}}的其他基金

The impact of ampicillin and breast milk oligosaccharides on the infant microbiome and immune functions
氨苄西林和母乳低聚糖对婴儿微生物组和免疫功能的影响
  • 批准号:
    10681295
  • 财政年份:
    2021
  • 资助金额:
    $ 70.58万
  • 项目类别:
The impact of ampicillin and breast milk oligosaccharides on the infant microbiome and immune functions
氨苄西林和母乳低聚糖对婴儿微生物组和免疫功能的影响
  • 批准号:
    10309710
  • 财政年份:
    2021
  • 资助金额:
    $ 70.58万
  • 项目类别:
The impact of ampicillin and breast milk oligosaccharides on the infant microbiome and immune functions
氨苄西林和母乳低聚糖对婴儿微生物组和免疫功能的影响
  • 批准号:
    10487500
  • 财政年份:
    2021
  • 资助金额:
    $ 70.58万
  • 项目类别:
C3-Dependent Intracellular Killing in Innate Immunity and Bacterial Pathogenesis
先天免疫和细菌发病机制中 C3 依赖性细胞内杀伤
  • 批准号:
    9765616
  • 财政年份:
    2019
  • 资助金额:
    $ 70.58万
  • 项目类别:
Glycan-Lectin Receptor Regulation of Macrophage Maturation and Lung Innate Defenses in the Fetus and Newborn Infant
胎儿和新生儿巨噬细胞成熟和肺先天防御的聚糖-凝集素受体调节
  • 批准号:
    9979752
  • 财政年份:
    2019
  • 资助金额:
    $ 70.58万
  • 项目类别:
C3-Dependent Intracellular Killing in Innate Immunity and Bacterial Pathogenesis
先天免疫和细菌发病机制中 C3 依赖性细胞内杀伤
  • 批准号:
    9886202
  • 财政年份:
    2019
  • 资助金额:
    $ 70.58万
  • 项目类别:
C3-Dependent Intracellular Killing in Innate Immunity and Bacterial Pathogenesis
先天免疫和细菌发病机制中 C3 依赖性细胞内杀伤
  • 批准号:
    10579831
  • 财政年份:
    2019
  • 资助金额:
    $ 70.58万
  • 项目类别:
C3-Dependent Intracellular Killing in Innate Immunity and Bacterial Pathogenesis
先天免疫和细菌发病机制中 C3 依赖性细胞内杀伤
  • 批准号:
    10357760
  • 财政年份:
    2019
  • 资助金额:
    $ 70.58万
  • 项目类别:
Glycan-Lectin Receptor Regulation of Macrophage Maturation and Lung InnateDefenses in the Fetus and Newborn Infant
胎儿和新生儿巨噬细胞成熟和肺先天防御的聚糖-凝集素受体调节
  • 批准号:
    10360375
  • 财政年份:
    2019
  • 资助金额:
    $ 70.58万
  • 项目类别:
C3-Dependent Intracellular Killing in Innate Immunity and Bacterial Pathogenesis
先天免疫和细菌发病机制中 C3 依赖性细胞内杀伤
  • 批准号:
    10094189
  • 财政年份:
    2019
  • 资助金额:
    $ 70.58万
  • 项目类别:

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血液转录组学作为 CT 佐剂排除急性中风出血
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