High-throughput experiments to guide influenza vaccine strain selection
高通量实验指导流感疫苗株选择
基本信息
- 批准号:9757688
- 负责人:
- 金额:$ 42.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-26 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAmino AcidsBig DataBiological AssayCell Culture TechniquesCessation of lifeCodon NucleotidesComputational TechniqueComputer SimulationDataDevelopmentEffectivenessEpidemicEpitopesErythrocytesEvolutionFerretsFrequenciesGenesGrowthHemagglutininHomologous GeneHumanImmune SeraImmunityInfluenzaInfluenza A Virus, H3N2 SubtypeInternetIntuitionLinkMeasurementMeasuresMembrane ProteinsMethodsModelingMutationNucleoproteinsPhylogenyPoint MutationPopulationProcessPropertyProteinsPublic HealthResearch PersonnelSeasonsSerumShapesSourceTechniquesTestingTimeVaccinationVaccinesViralVirusWorkcomputer codecomputerized toolscostdeep sequencingexperimental studyfitnesshomologous recombinationimprovedinfluenza virus vaccineinnovationmutantmutation screeningpredictive modelingpublic health interventionseasonal influenzatime usevaccine effectivenessvaccine efficacy
项目摘要
PROJECT SUMMARY
Every year, seasonal influenza infects 5-15% of the human population, resulting in over 250,000
deaths worldwide. The annual influenza vaccine is the primary public-health intervention against
these epidemics. The strains in the vaccine must be selected before the influenza season.
Unfortunately, the selected strains sometimes fail to closely match those that end up actually
circulating in the human population; such strain mismatches reduce vaccine efficacy. Methods
for better selecting vaccine strains are therefore of paramount importance to public health.
We will use innovative new experimental and computational techniques to guide better vaccine-
strain selection. Two key properties determine which influenza strains dominate a season:
successful strains have high inherent fitness (manifested by a low load of deleterious mutations)
and an abundance of antigenic mutations in the epitopes recognized by human immunity. We
will measure how each of these properties is affected by every possible amino-acid mutation to
the viral surface protein hemagglutinin. To make these high-throughput measurements, we will
generate pools of viruses carrying all possible codon mutations to hemagglutinin, and then
passage these mutant viruses in the presence and absence of human serum. We will then use
ultra-accurate deep sequencing to count the frequency of every mutation pre- and post-
selection, enabling us to quantify how each mutation affects both deleterious load and antigenic
recognition by serum from a cross-section of the human population.
To improve vaccine-strain selection, we will use a real-time web platform to overlay our
measurements of deleterious mutational load and the antigenic change onto an influenza
phylogeny. This platform will enable decision makers to intuitively visualize the “Big Data”
generated by our experiments as they weigh all sources of evidence during the strain-selection
process. In addition, we will make our data and computer code readily available, so that others
can leverage our work for their own efforts to better predict influenza strain dynamics.
This work has direct relevance to public health in that it will help guide better vaccine-strain
selection at a fraction of the cost of current approaches, and thereby improve seasonal influenza
vaccine effectiveness.
项目总结
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(1)
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 }}
Jesse D Bloom其他文献
Evolving strategies for enzyme engineering
- DOI:
10.1016/j.sbi.2005.06.004 - 发表时间:
2005-08-01 - 期刊:
- 影响因子:
- 作者:
Jesse D Bloom;Michelle M Meyer;Peter Meinhold;Christopher R Otey;Derek MacMillan;Frances H Arnold - 通讯作者:
Frances H Arnold
Jesse D Bloom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('Jesse D Bloom', 18)}}的其他基金
Prospectively characterizing the functional and antigenic effects of mutations to viral entry proteins
前瞻性地表征病毒进入蛋白突变的功能和抗原效应
- 批准号:
10593369 - 财政年份:2018
- 资助金额:
$ 42.36万 - 项目类别:
Prospectively characterizing the functional and antigenic effects of mutations to viral entry proteins
前瞻性地表征病毒进入蛋白突变的功能和抗原效应
- 批准号:
10237969 - 财政年份:2018
- 资助金额:
$ 42.36万 - 项目类别:
Complete mapping of immune selection from antibodies to HIV
从抗体到 HIV 的免疫选择的完整图谱
- 批准号:
10305599 - 财政年份:2018
- 资助金额:
$ 42.36万 - 项目类别:
Complete mapping of immune selection from antibodies to HIV
从抗体到 HIV 的免疫选择的完整图谱
- 批准号:
10059172 - 财政年份:2018
- 资助金额:
$ 42.36万 - 项目类别:
Prospectively characterizing the functional and antigenic effects of mutations to viral entry proteins
前瞻性地表征病毒进入蛋白突变的功能和抗原效应
- 批准号:
10471843 - 财政年份:2018
- 资助金额:
$ 42.36万 - 项目类别:
Complete mapping of immune selection from antibodies to HIV
从抗体到 HIV 的免疫选择的完整图谱
- 批准号:
10540820 - 财政年份:2018
- 资助金额:
$ 42.36万 - 项目类别:
Prospectively characterizing the functional and antigenic effects of mutations to viral entry proteins
前瞻性地表征病毒进入蛋白突变的功能和抗原效应
- 批准号:
9790939 - 财政年份:2018
- 资助金额:
$ 42.36万 - 项目类别:
Complete mapping of immune selection from antibodies to HIV
从抗体到 HIV 的免疫选择的完整图谱
- 批准号:
10593442 - 财政年份:2018
- 资助金额:
$ 42.36万 - 项目类别:
High-throughput experiments to guide influenza vaccine strain selection
高通量实验指导流感疫苗株选择
- 批准号:
9219103 - 财政年份:2016
- 资助金额:
$ 42.36万 - 项目类别:
相似海外基金
Double Incorporation of Non-Canonical Amino Acids in an Animal and its Application for Precise and Independent Optical Control of Two Target Genes
动物体内非规范氨基酸的双重掺入及其在两个靶基因精确独立光学控制中的应用
- 批准号:
BB/Y006380/1 - 财政年份:2024
- 资助金额:
$ 42.36万 - 项目类别:
Research Grant
Quantifying L-amino acids in Ryugu to constrain the source of L-amino acids in life on Earth
量化 Ryugu 中的 L-氨基酸以限制地球生命中 L-氨基酸的来源
- 批准号:
24K17112 - 财政年份:2024
- 资助金额:
$ 42.36万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Molecular recognition and enantioselective reaction of amino acids
氨基酸的分子识别和对映选择性反应
- 批准号:
23K04668 - 财政年份:2023
- 资助金额:
$ 42.36万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Basic research toward therapeutic strategies for stress-induced chronic pain with non-natural amino acids
非天然氨基酸治疗应激性慢性疼痛策略的基础研究
- 批准号:
23K06918 - 财政年份:2023
- 资助金额:
$ 42.36万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular mechanisms how arrestins that modulate localization of glucose transporters are phosphorylated in response to amino acids
调节葡萄糖转运蛋白定位的抑制蛋白如何响应氨基酸而被磷酸化的分子机制
- 批准号:
23K05758 - 财政年份:2023
- 资助金额:
$ 42.36万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Design and Synthesis of Fluorescent Amino Acids: Novel Tools for Biological Imaging
荧光氨基酸的设计与合成:生物成像的新工具
- 批准号:
2888395 - 财政年份:2023
- 资助金额:
$ 42.36万 - 项目类别:
Studentship
Collaborative Research: RUI: Elucidating Design Rules for non-NRPS Incorporation of Amino Acids on Polyketide Scaffolds
合作研究:RUI:阐明聚酮化合物支架上非 NRPS 氨基酸掺入的设计规则
- 批准号:
2300890 - 财政年份:2023
- 资助金额:
$ 42.36万 - 项目类别:
Continuing Grant
Structurally engineered N-acyl amino acids for the treatment of NASH
用于治疗 NASH 的结构工程 N-酰基氨基酸
- 批准号:
10761044 - 财政年份:2023
- 资助金额:
$ 42.36万 - 项目类别:
Lifestyle, branched-chain amino acids, and cardiovascular risk factors: a randomized trial
生活方式、支链氨基酸和心血管危险因素:一项随机试验
- 批准号:
10728925 - 财政年份:2023
- 资助金额:
$ 42.36万 - 项目类别:
Single-molecule protein sequencing by barcoding of N-terminal amino acids
通过 N 端氨基酸条形码进行单分子蛋白质测序
- 批准号:
10757309 - 财政年份:2023
- 资助金额:
$ 42.36万 - 项目类别: