Development of broadly-protective vaccines for influenza B viruses
开发针对乙型流感病毒的广泛保护性疫苗
基本信息
- 批准号:10206685
- 负责人:
- 金额:$ 22.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-02-25 至 2023-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdjuvantAffectAlhydrogelAnimalsAntibodiesAntibody titer measurementAntigensAttenuated VaccinesBacteriophagesBiological AssayCD8-Positive T-LymphocytesCellsComplementControl AnimalDataDevelopmentEpidemicEpitopesFerretsFutureHemagglutininHumanImmune responseImmunityImmunizationImmunizeImmunologyInfectionInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H3N2 SubtypeInfluenza A virusInfluenza B VirusLeadLibrariesLung diseasesMapsMorbidity - disease rateMutagenesisMutationOrganPeptidesPhage DisplayPharmaceutical PreparationsPhasePopulationPropertyProteinsRecombinantsResearchSaint Jude Children&aposs Research HospitalSerumSpleenTestingUpdateVaccinatedVaccinationVaccinesVariantViral AntigensViral ProteinsVirusbasecross reactivitycytokinedesignexperimental studyimmunogenicityimprovedinfluenza virus straininfluenza virus vaccineinfluenzaviruslymph nodesmortalitymutantnanoparticlenovelnovel strategiesprotective efficacyrespiratoryresponsestemuniversal vaccinevaccine accessvaccine candidatevaccine efficacy
项目摘要
PROJECT SUMMARY
Influenza B viruses (IBV) cause annual epidemics with appreciable morbidity and mortality, but have been
understudied compared to influenza A viruses (IAV). Currently available vaccines for IBV and IAV are sub-
optimal and must be updated frequently due to the emergence of novel antigenic variants. To date, efforts to
develop broadly protective, potentially ‘universal’ vaccines have almost exclusively focused on IAV. RFA-AI-20-
003 therefore calls for the “development and/or characterization of IBV vaccine components that
complement existing lead IAV vaccine candidates”. In Aim 1 (R21 phase), we plan to develop broadly reactive
influenza B candidate vaccine viruses. Using mutagenesis approaches, we have already generated mutant
IBV hemagglutinins (HA, the major viral antigen) whose antigenic properties are in-between those of the two
major lineages of IBV. Thus, these antigens may elicit immune responses that confer protection against viruses
of both IBV lineages. Here, we plan to develop additional IBV HA mutants with potentially higher cross-reactivity
than that of our current candidates. In addition, we will establish an antigenic map for IBV HA to analyze the
antigenic properties of IBV HAs (antigenic maps are now widely used for IAV HAs, but have not been developed
for IBV HA). In Aim 2 (R33 phase), we will assess the immunogenicity of influenza B candidate vaccine
viruses. Briefly, the top 5 candidates from Aim 1 will be used to immunize ferrets. Immunization will be carried
out with adjuvanted, secreted IBV HA (sHA) mutants (thus eliminating the contribution of other IBV proteins to
immune responses), or with adjuvanted IBV HA presented on nanoparticles composed of a self-assembling
phage protein (generated by Dr. R. Kane, Georgia Tech). The sera from vaccinated ferrets will be tested for
reactivity with IBV HA antigens, and these data will be integrated into the antigenic map. Using an established
phage display approach, Dr. S. Khurana (Federal Drug Administration) will identify the epitopes targeted by the
antibodies elicited by our HA mutants. This analysis will allow us to identify antigens that elicit broadly reactive
antibodies that target conserved epitopes. Immunology studies will be carried out by Dr. P. Thomas, St. Jude
Children’s Research Hospital. On the basis of the data obtained in Aim 2, the top 2 IBV HA immunogens will be
used to assess the protective efficacy of influenza B candidate vaccine viruses (Aim 3, R33 phase). Ferrets
will be immunized as established in Aim 2 and challenged with IBVs representing both current lineages and an
ancestral virus (isolated before the separation of the lineages). Virus titers and immune responses will be
compared with those of control animals. We expect that a single immunization with the IBV HA mutants will elicit
more broadly protective immunity than a single immunization with wild-type IBV HA. In summary, upon
completion of both phases, we expect to have developed a novel strategy for the design of broadly protective
IBV vaccines, and to have demonstrated their broadly protective efficacy in ferrets.
项目总结
项目成果
期刊论文数量(0)
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YOSHIHIRO KAWAOKA其他文献
YOSHIHIRO KAWAOKA的其他文献
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{{ truncateString('YOSHIHIRO KAWAOKA', 18)}}的其他基金
Development of broadly-protective vaccines for influenza B viruses
开发针对乙型流感病毒的广泛保护性疫苗
- 批准号:
10821572 - 财政年份:2023
- 资助金额:
$ 22.78万 - 项目类别:
Development of broadly-protective vaccines for influenza B viruses
开发针对乙型流感病毒的广泛保护性疫苗
- 批准号:
10359831 - 财政年份:2021
- 资助金额:
$ 22.78万 - 项目类别:
COVID-19 comorbidity studies in Syrian hamster models
叙利亚仓鼠模型中的 COVID-19 合并症研究
- 批准号:
10450889 - 财政年份:2021
- 资助金额:
$ 22.78万 - 项目类别:
PanCorVac (Center for Pan-Coronavirus Vaccine Development)
PanCorVac(泛冠状病毒疫苗开发中心)
- 批准号:
10841731 - 财政年份:2021
- 资助金额:
$ 22.78万 - 项目类别:
COVID-19 comorbidity studies in Syrian hamster models
叙利亚仓鼠模型中的 COVID-19 合并症研究
- 批准号:
10285154 - 财政年份:2021
- 资助金额:
$ 22.78万 - 项目类别:
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