Development of vaccine approaches to elicit broadly protective influenza-specific immune responses in infants
开发疫苗方法以在婴儿中引发广泛保护性的流感特异性免疫反应
基本信息
- 批准号:10229523
- 负责人:
- 金额:$ 73.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-05 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:1 year oldAddressAdjuvantAdultAffinityAfrican Green MonkeyAge-MonthsAgonistAnimal ModelAntibodiesAntibody FormationAntibody ResponseAntigensAreaB cell differentiationB-LymphocytesBiological AssayCellsCenters for Disease Control and Prevention (U.S.)ChildDataDevelopmentDiseaseDoseEffectivenessGenerationsGoalsHospitalizationHumanImmuneImmune responseImmune systemImmunoglobulin GIndividualInfantInfluenzaInfluenza vaccinationInterferon Type IIInvestigationLeadLifeLigandsLower Respiratory Tract InfectionMF59MaintenanceMaternal antibodyMeasuresMemory B-LymphocyteModelingMusNational Institute of Allergy and Infectious DiseaseNewborn InfantOX40PopulationPositioning AttributeResearchRiskRoleSignal TransductionSpecificityStructure of germinal center of lymph nodeT cell responseTLR7 geneTestingTimeVaccinatedVaccinationVaccine DesignVaccinesVirusVulnerable PopulationsWorkadaptive immune responseage groupbaseimmunogenicityimprovedinfancyinfant animalinfluenza infectioninfluenza virus straininfluenza virus vaccineinfluenzavirusnanoparticleneonatenonhuman primatepre-clinicalresponsestemuniversal influenza vaccineuniversal vaccinevaccine accessvaccine candidatevaccine developmentvaccine responsevaccine safety
项目摘要
Influenza virus infection of neonates can lead to life-threatening disease. The rate of LRTI-associated
hospitalizations is >4 times higher in children less than 1 year of age compared to those between 1 and 4
years and infants younger than 6 months of age are particularly vulnerable to the development of severe
disease. Current influenza vaccines on the market are not approved for infants <6 months of age as a result of
their limited effectiveness in this age group. Overcoming this poor responsiveness will require development of
vaccines with greater immunogenicity in this population. Another important area of investigation is the ability of
infants to respond to universal vaccines designed to provide protection across multiple strains of influenza.
While targeting production of these antibodies by vaccination is highly desirable, our understanding of how
effectively newborns can produce them or the accessory signals that can optimally elicit these antibodies is
unknown. The ultimate goal of the studies proposed in this application is to identify a vaccine approach for
influenza that is safe and broadly protective when delivered to neonates. To evaluate potential strategies, we
will use our established African green monkey (AGM) nonhuman primate neonate model. Using this model we
previously found that conjugation of the TLR7/8 agonist R848 to inactivated influenza promotes significant
increases in virus-specific IgG and IFNγ-producing T cell responses, providing rationale for the continued
exploration of this adjuvant in neonates. We will utilize R848 together with heterologous boost or an HA stem
construct as approaches to elicit broadly reactive antibody. As part of our analyses we will evaluate the role of
Tfh responses in modulating broadly reactive antibody quantity and quality. The results of these studies will
provide mechanistic as well as practical information that may lead to the improved design of vaccines that will
be efficacious in the vulnerable neonate population.
新生儿感染流感病毒可导致危及生命的疾病。与LRTI相关的比率
1岁以下儿童的住院率是1岁至4岁儿童的4倍
6岁和6个月以下的婴儿特别容易患上严重的
疾病。目前市场上的流感疫苗没有被批准用于6个月大的婴儿和婴儿,因为
他们在这个年龄段的效果有限。克服这种糟糕的响应性将需要开发
在这一人群中具有更强免疫原性的疫苗。另一个重要的调查领域是
婴儿对通用疫苗做出反应,该疫苗旨在为多种流感病毒株提供保护。
虽然通过接种疫苗来靶向产生这些抗体是非常可取的,但我们对如何
有效地,新生儿可以产生它们,或者可以最佳地诱导这些抗体的辅助信号是
未知。本申请中提出的研究的最终目标是确定一种疫苗方法
当传染给新生儿时是安全和广泛保护的流感。为了评估潜在的战略,我们
将使用我们建立的非洲绿猴(AGM)非人类灵长类新生儿模型。使用此模型,我们
先前发现,TLR7/8激动剂R848与灭活流感的结合显著促进了
病毒特异性免疫球蛋白和干扰素γ产生的T细胞反应增加,为继续
探索这种佐剂在新生儿中的应用。我们将结合使用R848和异源Boost或HA茎
构建作为诱导广泛反应性抗体的方法。作为我们分析的一部分,我们将评估
TFH在调节广谱反应性抗体数量和质量方面的反应。这些研究的结果将
提供可能导致改进疫苗设计的机械和实用信息,从而
对脆弱的新生儿群体有效。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Martha Ann Alexander-Miller其他文献
Martha Ann Alexander-Miller的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Martha Ann Alexander-Miller', 18)}}的其他基金
Development of vaccine approaches to elicit broadly protective influenza-specific immune responses in infants
开发疫苗方法以在婴儿中引发广泛保护性的流感特异性免疫反应
- 批准号:
10456073 - 财政年份:2020
- 资助金额:
$ 73.91万 - 项目类别:
Vaccination strategies to overcome immune deficiencies in neonates
克服新生儿免疫缺陷的疫苗接种策略
- 批准号:
8840143 - 财政年份:2012
- 资助金额:
$ 73.91万 - 项目类别:
Vaccination strategies to overcome immune deficiencies in neonates
克服新生儿免疫缺陷的疫苗接种策略
- 批准号:
8477124 - 财政年份:2012
- 资助金额:
$ 73.91万 - 项目类别:
Vaccination strategies to overcome immune deficiencies in neonates
克服新生儿免疫缺陷的疫苗接种策略
- 批准号:
8668895 - 财政年份:2012
- 资助金额:
$ 73.91万 - 项目类别:
Vaccination strategies to overcome immune deficiencies in neonates
克服新生儿免疫缺陷的疫苗接种策略
- 批准号:
8319130 - 财政年份:2012
- 资助金额:
$ 73.91万 - 项目类别:
Cellular Immune Responses to Respiratory Infection
对呼吸道感染的细胞免疫反应
- 批准号:
7371984 - 财政年份:2004
- 资助金额:
$ 73.91万 - 项目类别:
Cellular Immune Responses to Respiratory Infection
对呼吸道感染的细胞免疫反应
- 批准号:
6867421 - 财政年份:2004
- 资助金额:
$ 73.91万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 73.91万 - 项目类别:
Research Grant