Wild-type allele found in varicella vaccine virus during severe herpes zoster
严重带状疱疹期间水痘疫苗病毒中发现野生型等位基因
基本信息
- 批准号:10038935
- 负责人:
- 金额:$ 22.68万
- 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:2020-05-21 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcyclovirAdmission activityAdverse eventAllelesApplications GrantsArginineArvinAsiansAsthmaAttenuatedAttenuated Live Virus VaccineAutoimmune DiseasesCessation of lifeChickenpoxChickenpox VaccineChildCountryDataDiseaseEuropeanExanthemaFDA approvedGenesGenetic PolymorphismGenomeGoalsGrantHearingHerpes zoster diseaseImmunizeImmunocompetentInfectionInjectionsIowaJournalsLeadLeftMutateMutationNorth AmericaNucleotidesOpen Reading FramesPatientsPediatric NeurologyPhysiciansProteinsReportingResearchResearch PersonnelRisk FactorsRoleSCID MiceScientistSecondary toSiteSkinSpinal GangliaStructureTerminator CodonThigh structureTransverse MyelitisTravelUnited StatesVZV vaccineVaccinationVaccine DesignVaccinesVariantViralViremiaVirulenceVirulentVirusVirus DiseasesWorkafferent nerveattenuationbasedermatomeimprovedmouse modelside effectvaccine safetyvaricella-zoster virus glycoprotein gp1varicella-zoster virus immediate early protein 62virtualwhole genome
项目摘要
This grant proposal is submitted under PA-18-872 Research to advance vaccine safety. The impetus for this
R21 grant proposal is a recent report from this lab in the Journal of Child Neurology 2019. The title of the
article: Severe herpes zoster following varicella vaccination of immunocompetent young children. The
hypothesis for this proposal is that VZV ORF0 is a major determinant of attenuation in the live varicella vaccine
vOka; further, a variant of the current vaccine product that contains the wild-type ORF0 allele rather than the
attenuated ORF0 allele is more likely to reactivate as severe herpes zoster. My lab and a Canadian lab made a
critical discovery about VZV attenuation after we sequenced the entire genome of the well-known Ellen lab
strain. We had previously shown, using the Arvin lab’s SCID mouse model, that the Ellen strain was even
more attenuated than the Oka vaccine strain. When we compared the complete sequence of Ellen and vOka,
we made a completely unpredictable discovery. The two strains had common SNPs in IE62 gene, as
expected. What was not expected was the discovery that the Ellen lab strain (a wild type strain isolated in
Georgia in the 1960s) had a vaccine-type ORF0 gene. Unbeknownst to VZV researchers, therefore, the Ellen
strain had acquired polymorphisms in both IE62 (ORF62) and ORF0 that were extremely similar to the vaccine
strain. The goal of the R21 grant is to initiate studies to define ORF0 as an important determinant of
attenuation in the VZV vaccine. Essentially, therefore, this grant proposes that the virologists who first made
the live varicella vaccine in the 1970’s omitted a step in the late design of the vaccine, which allowed a more
virulent variant to be included in the final vaccine product. The research plan includes two specific aims and
also includes two consultants. The importance of this research has vaccine safety relevance. There have
been thousands of reports of adverse event after varicella vaccination, including death from disseminated
vaccine virus infection. Since the original stocks of vaccine virus were never cloned by the Takahashi lab in
Osaka, the current commercial vaccine product contains a variant with wild-type ORF0 allele. We suggest that
the vaccine subspecies or variant with wild-type ORF0 may be causing many of the severe side effects
following varicella vaccination.
该拨款提案根据 PA-18-872 研究提交,旨在提高疫苗安全性。这样做的动力
R21 资助提案是该实验室最近在《2019 年儿童神经病学杂志》上发表的一份报告。
文章:免疫功能健全的幼儿接种水痘疫苗后出现严重带状疱疹。这
该提议的假设是 VZV ORF0 是水痘活疫苗减毒的主要决定因素
沃卡;此外,当前疫苗产品的变体包含野生型 ORF0 等位基因,而不是
减弱的 ORF0 等位基因更有可能重新激活为严重的带状疱疹。我的实验室和加拿大实验室做了一个
在我们对著名的 Ellen 实验室的整个基因组进行测序后,关于 VZV 减弱的重要发现
拉紧。我们之前使用 Arvin 实验室的 SCID 小鼠模型证明,Ellen 品系甚至
比 Oka 疫苗株的减毒效果更强。当我们比较 Ellen 和 vOka 的完整序列时,
我们有了一个完全不可预测的发现。两株菌株的IE62基因具有共同的SNP,
预期的。出乎意料的是,我们发现艾伦实验室菌株(一种在
20世纪60年代的乔治亚州)有一个疫苗型ORF0基因。因此,VZV 研究人员不知道的是,Ellen
该菌株在 IE62 (ORF62) 和 ORF0 中获得了与疫苗极其相似的多态性
拉紧。 R21 资助的目标是启动研究,将 ORF0 定义为重要的决定因素
VZV 疫苗的减毒作用。因此,从本质上讲,这笔赠款建议首先进行研究的病毒学家
1970 年代的水痘活疫苗省略了疫苗后期设计中的一个步骤,这使得更多
将包含在最终疫苗产品中的强毒变体。该研究计划包括两个具体目标
还包括两名顾问。这项研究的重要性与疫苗安全相关。有
已有数千份关于水痘疫苗接种后不良事件的报告,包括传播性死亡
疫苗病毒感染。由于高桥实验室从未克隆出最初的疫苗病毒库存
大阪目前的商业疫苗产品含有带有野生型 ORF0 等位基因的变体。我们建议
具有野生型 ORF0 的疫苗亚种或变体可能会引起许多严重的副作用
接种水痘疫苗后。
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 }}
Charles F. Grose其他文献
Charles F. Grose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('Charles F. Grose', 18)}}的其他基金
Autophagy and ER stress during varicella infection
水痘感染期间的自噬和内质网应激
- 批准号:
8427354 - 财政年份:2011
- 资助金额:
$ 22.68万 - 项目类别:
Autophagy and ER stress during varicella infection
水痘感染期间的自噬和内质网应激
- 批准号:
8232048 - 财政年份:2011
- 资助金额:
$ 22.68万 - 项目类别:
Autophagy and ER stress during varicella infection
水痘感染期间的自噬和内质网应激
- 批准号:
8803757 - 财政年份:2011
- 资助金额:
$ 22.68万 - 项目类别:
Autophagy and ER stress during varicella infection
水痘感染期间的自噬和内质网应激
- 批准号:
8101645 - 财政年份:2011
- 资助金额:
$ 22.68万 - 项目类别:
ACQUISITION OF HUMAN HERPES VIRUS-8 IN INFANCY
在婴儿期获得人类疱疹病毒 8
- 批准号:
7604837 - 财政年份:2007
- 资助金额:
$ 22.68万 - 项目类别:
IMMUNOSCANNING ELECTRON MICROSCOPY OF HERPES VIRUSES
疱疹病毒的免疫扫描电子显微镜
- 批准号:
6278480 - 财政年份:1998
- 资助金额:
$ 22.68万 - 项目类别:
IMMUNOSCANNING ELECTRON MICROSCOPY OF HERPES VIRUSES
疱疹病毒的免疫扫描电子显微镜
- 批准号:
6117285 - 财政年份:1998
- 资助金额:
$ 22.68万 - 项目类别:
DNA SEQUENCING--ITERATIVE STEPS BY PRODUCT REGENERATION
DNA 测序——产物再生的迭代步骤
- 批准号:
2889694 - 财政年份:1998
- 资助金额:
$ 22.68万 - 项目类别: