Induction of cross C. trachomatis serovar protection utilizing a polyvalent nanoparticle vaccine.
利用多价纳米颗粒疫苗诱导交叉沙眼衣原体血清型保护。
基本信息
- 批准号:10223115
- 负责人:
- 金额:$ 38.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-08 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:Abdominal PainAcuteAdjuvantAnimalsAntibioticsAntibodiesAntigensAreaBioinformaticsBiologicalBlindnessC3H/HeN MouseCellsChlamydia InfectionsChlamydia muridarumChlamydia trachomatisChronicClassificationComplexCountryDNADNA sequencingDataDiseaseEctopic PregnancyEmbryoEngineeringEye InfectionsFemaleFertilityGenitalGenitaliaGoalsHealthHumanImmune responseImmunizationImmunizeImmunologic MemoryImmunologyIn VitroInfectionInfertilityLengthLicensureLipoproteinsLymphogranuloma VenereumMediatingMembrane ProteinsMessenger RNAModelingMolecular ConformationMucous MembraneMusPartner in relationshipPathogenesisPathologyPelvic Inflammatory DiseasePeptidesPhylogenetic AnalysisPolyvalent VaccineProductionProteinsRNARecombinant VaccinesRecombinantsResearch Project GrantsRespiratory SystemRespiratory Tract InfectionsRouteSafetySerologySerumSeveritiesSexual TransmissionSexually Transmitted DiseasesSubunit VaccinesT-LymphocyteTestingTimeTrachomaTreesVaccinatedVaccinationVaccine ProductionVaccinesVaginaWomanbasechlamydia vaccinechronic abdominal painclinically relevantcytokineeffectiveness evaluationgastrointestinal systemgenital infectionhealth economicsimmunogenicitymajor outer membrane proteinmalemennanonanolipoprotein particlesnanoparticlenonhuman primateparticlepathogenic bacteriapregnantreproductive tractrespiratoryscaffoldscale upsocioeconomicsvaccination outcomevaccine developmentvaccine effectivenessvaccine trial
项目摘要
ABSTRACT
Throughout the world Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial
pathogen. In countries with poor sanitary conditions ocular infections with Ct can result in trachoma, the most
frequent cause of preventable blindness worldwide. Based on protection and serological studies in mice Ct is
classified into 15 major serovars of which eight account for most of the sexually transmitted infections (STI). In
men and women, the majority of genital Ct infections are asymptomatic and therefore not treated. Even in
symptomatic cases unless therapy is implemented in a timely and correct manner long-term sequelae including
pelvic inflammatory disease (PID), chronic abdominal pain, ectopic pregnancy and infertility can occur. Thus,
vaccination is the best approach to control chlamydial infections. In this Project we want to test the hypothesis
that a subunit vaccine formulated with Ct antigens elicits robust immune responses and induces cross-serovar
protection in female mice against a genital challenge. To accomplish this goal we are going to test, in C3H/HeN
female mice, vaccines formulated with the Ct major outer membrane protein (MOMP) and the polymorphic
membrane proteins (Ppms). MOMP, MOMP peptides, MOMP DNA and RNA, from Ct senior serovars, will be
formulated and delivered using Nano-Scaffold-Based Nano Lipoprotein Particles (NLP). Immunization with
native MOMP will help guide the production of these vaccine constructs. To enhance protection in the genital
tract, mice will be vaccinated by mucosal and systemic routes using adjuvants. Following vaccination, mucosal
and systemic cellular and humoral immune responses will be determined and correlated with protection.
Vaccinated animals will be challenged transcervically with the eight most clinically relevant Ct serovars.
Protection against infection will be assessed by determining the number of mice with positive vaginal cultures,
the total number of positive vaginal cultures, the length of time mice shed and the severity of vaginal shedding.
To determine protection against long-term sequelae vaccinated and challenged female mice will subsequently
be caged with proven male breeder mice and fertility and upper genital pathology, including hydrosalpinx
formation, will be evaluated. If we cannot obtain a robust, broad cross-serovar protection by vaccinating only
with MOMP, we will test a polyvalent vaccine with MOMP in combination with Ppm C, G or H using NLP. To
ascertain the neutral, additive, synergistic, or antagonistic effects of each antigen, following vaccination,
immune responses to each antigen will be characterized and the data will be correlated with protection. Our
goal is to engineer a safe Nano-Scaffold-Based subunit vaccine that protects mice against a genital challenge
with the Ct serovars that infect the human genital tract. At the end of this project protective vaccine constructs
will be ready for scale-up production and human implementation. An efficacious vaccine against Ct will have a
broad worldwide health and socioeconomic impact.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Matthew Adrian Coleman其他文献
Matthew Adrian Coleman的其他文献
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{{ truncateString('Matthew Adrian Coleman', 18)}}的其他基金
Project 1. Nanolipoprotein-supported multi-subunit vaccine for Chlamydia trachomatis
项目1.纳米脂蛋白支持的沙眼衣原体多亚单位疫苗
- 批准号:
10223114 - 财政年份:2019
- 资助金额:
$ 38.36万 - 项目类别:
Induction of cross C. trachomatis serovar protection utilizing a polyvalent nanoparticle vaccine.
利用多价纳米颗粒疫苗诱导交叉沙眼衣原体血清型保护。
- 批准号:
10458656 - 财政年份:2019
- 资助金额:
$ 38.36万 - 项目类别:
Cooperative Research Center for NanoScaffold-Based Chlamydia trachomatis Vaccines - Admin Core
基于纳米支架的沙眼衣原体疫苗合作研究中心 - 管理核心
- 批准号:
10458650 - 财政年份:2019
- 资助金额:
$ 38.36万 - 项目类别:
Center for Biologically Inspired Nano-scaffolds for Mitigating Chlamydia trachomatis Pathogenesis
减轻沙眼衣原体发病机制的生物启发纳米支架中心
- 批准号:
10458649 - 财政年份:2019
- 资助金额:
$ 38.36万 - 项目类别:
Project 1. Nanolipoprotein-supported multi-subunit vaccine for Chlamydia trachomatis
项目1.纳米脂蛋白支持的沙眼衣原体多亚单位疫苗
- 批准号:
10458654 - 财政年份:2019
- 资助金额:
$ 38.36万 - 项目类别:
Center for Biologically Inspired Nano-scaffolds for Mitigating Chlamydia trachomatis Pathogenesis
减轻沙眼衣原体发病机制的生物启发纳米支架中心
- 批准号:
10223108 - 财政年份:2019
- 资助金额:
$ 38.36万 - 项目类别:
Cooperative Research Center for NanoScaffold-Based Chlamydia trachomatis Vaccines - Admin Core
基于纳米支架的沙眼衣原体疫苗合作研究中心 - 管理核心
- 批准号:
10223110 - 财政年份:2019
- 资助金额:
$ 38.36万 - 项目类别:
Characterization of Erbb Receptors in Nanoparticles
纳米颗粒中 Erbb 受体的表征
- 批准号:
8504801 - 财政年份:2011
- 资助金额:
$ 38.36万 - 项目类别:
Characterization of Erbb Receptors in Nanoparticles
纳米颗粒中 Erbb 受体的表征
- 批准号:
8678706 - 财政年份:2011
- 资助金额:
$ 38.36万 - 项目类别:
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