Development of polyvalent inactivated rhinovirus vaccine
Development of polyvalent inactivated rhinovirus vaccine
批准号:
9342637
负责人:
Martin Lawrence Moore
金额:
$21.64万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-04-01 至 2018-06-30
关键词:
3&apos Untranslated Regions5&apos Untranslated RegionsAcuteAcute DiseaseAddressAdjuvantAdultAlhydrogelAlpha CellAntibody ResponseAntigensAsthmaBacterial Artificial ChromosomesBiologicalBiological AssayBiotechnologyBlood CirculationCapsidCapsid ProteinsCell LineCellsChemistryChildChronic Obstructive Airway DiseaseClinicalCommon ColdCommon Cold VirusCommunicable DiseasesCommunitiesComplementary DNAComplexComplex MixturesCyclic GMPDataDevelopmentDiseaseEnsureEquilibriumEtiologyFamily PicornaviridaeFormulationFutureGPA33 geneGenetic TranscriptionGenomeGoalsHospitalizationHumanImmunityIn VitroLaboratoriesLaboratory StudyLengthLiquid ChromatographyMacaca mulattaMass Spectrum AnalysisMeasurableMeasuresMedicalMethodsMusPeptidesPlayPneumoniaPolyproteinsPolyvalent VaccinePreparationProceduresProcessProteinsProteomicsPublishingRecombinantsRecording of previous eventsResearchResearch PersonnelRhinovirusRoleSeedsSeriesSerotypingSerumSystemT7 RNA polymeraseTestingTimeTransfectionUnited StatesUniversitiesVaccinesVirusWorkaluminum sulfateassay developmentbasecGMP productioncostdesignhigh risk populationimmunogenicityin vitro Assayinnovationmonolayerneutralizing antibodynonhuman primateplasmid DNAproduct developmentresearch clinical testingscale uptandem mass spectrometrytissue culturevaccine developmentviral RNA
中文摘要
人鼻病毒(RV)是普通感冒的主要病原,也是引起感冒的主要原因
英文摘要
Human rhinovirus (RV) is the predominant etiological agent of the common cold and the leading cause of
human infectious disease. RV is more than a nuisance. It is a major cause of community-acquired pneumonia
in children and adults in the United States and plays a major role in triggering exacerbations of both asthma
and chronic obstructive pulmonary disease, resulting in billions of dollars in medical costs every year in these
high-risk populations. Decades ago, researchers identified inactivated RV as a protective vaccine, defined
virus-neutralizing antibodies (nAb) as a correlate of protection against colds, and estimated duration of RV
immunity using monovalent inactivated RV. However, co-circulation of many RV types discouraged further
vaccine development. A 10-valent inactivated RV vaccine was tested in people in the 1970s, but only one-third
of the vaccine strains induced measurable nAb, reinforcing pessimism for RV vaccine development. However,
the average amount of each input RSV type antigen in this early 10-valent vaccine was low.
The Moore laboratory at Emory recently published that serum nAb against many RV types can be
induced by polyvalent inactivated RV adjuvanted with alum by simply increasing the amount of each RV
antigen in the vaccine. Using formulations up to 25-valent in mice and 50-valent in non-human primates,
inactivated RV vaccine immunogenicity was related to sufficient quantity of input antigens. Serum nAb to
polyvalent inactivated RV were type-specific, necessitating a high number of valences (RV types). These
proof-of-principle data point to a tractable vaccine approach for RV vaccine product development.
Highly polyvalent vaccine development will require overcoming challenges in chemistry, manufacturing,
and controls (CMC), such as identifying and ensuring potency and consistency of highly complex vaccine
mixtures. There are three RV species, A, B, and C, with 83, 32, and 55 types, respectively. There is no
evidence of RV antigenic drift. Meissa Vaccines, Inc and Emory University will initially focus on the most
prevalent RV types, the 83 types within species A. In order to balance manageable CMC research with product
development, our initial goal is to generate a 28-valent recombinant RV A vaccine. A 28-valent RV A vaccine
process and control can later be either scaled up and adapted to higher valency or, alternatively, be developed
as a series of three 28-valent vaccines, to cover all 83 RV A serotypes. In Aim 1, we will generate 28 RV A
infectious clone constructs harboring the capsid proteins of types A10, A12, A15, A16, A19, A28, A29, A31,
A32, A33, A34, A38, A40, A41, A49, A53, A55, A56, A58, A59, A60, A66, A68, A75, A78, A80, A85, or A96
and evaluate their ability to produce infectious virus in a cell line suitable for cGMP manufacturing. In Aim 2, we
will develop a proteomics-based assay to identify and quantify unique peptides corresponding to each of the 28
types in the 28-valent vaccine composition. This assay will be advanced for measuring potency of a highly
complex vaccine mixture and be assessed for ability to be qualified for releasing lots.
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批准号:9410335
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资助金额:$22.41万
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财政年份:2017
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负责人:Martin Lawrence Moore
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批准号:8000539
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资助金额:$30.0万
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财政年份:2010
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Role of the Respiratory Syncytial Virus Fusion Protein in Airway Mucus Induction
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批准号:8068877
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资助金额:$38.67万
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财政年份:2010
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负责人:Martin Lawrence Moore
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依托单位:
Role of the Respiratory Syncytial Virus Fusion Protein in Airway Mucus Induction
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批准号:8462893
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项目类别:
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资助金额:$35.98万
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财政年份:2010
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负责人:Martin Lawrence Moore
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Role of the Respiratory Syncytial Virus Fusion Protein in Airway Mucus Induction
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批准号:7866348
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项目类别:
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资助金额:$39.66万
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财政年份:2010
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负责人:Martin Lawrence Moore
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依托单位:
Role of the Respiratory Syncytial Virus Fusion Protein in Airway Mucus Induction
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批准号:8259817
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项目类别:
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资助金额:$38.28万
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财政年份:2010
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负责人:Martin Lawrence Moore
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依托单位:
Mechanisms of Respiratory Syncytial Virus-Induced Mucus" Viral Strain Dependence
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批准号:7772293
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项目类别:
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资助金额:$10.72万
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财政年份:2009
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负责人:Martin Lawrence Moore
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依托单位:
Mechanisms of Respiratory Syncytial Virus-Induced Mucus" Viral Strain Dependence
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批准号:7530495
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项目类别:
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资助金额:$15.69万
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财政年份:2009
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负责人:Martin Lawrence Moore
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依托单位:
Respiratory syncytial virus strain differences in bronchiolits and asthma
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批准号:9269761
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:Martin Lawrence Moore
-
依托单位:
Respiratory syncytial virus strain differences in bronchiolits and asthma
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批准号:8381083
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项目类别:
-
资助金额:$48.51万
-
财政年份:--
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负责人:Martin Lawrence Moore
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依托单位:
Respiratory syncytial virus strain differences in bronchiolits and asthma
-
批准号:8705258
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项目类别:
-
资助金额:$63.39万
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财政年份:--
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负责人:Martin Lawrence Moore
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依托单位:
Respiratory syncytial virus strain differences in bronchiolits and asthma
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批准号:8511339
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项目类别:
-
资助金额:$50.37万
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财政年份:--
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负责人:Martin Lawrence Moore
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依托单位:
海外基金