Pre-clinical evaluation of a Zika virus vaccine
Pre-clinical evaluation of a Zika virus vaccine
批准号:
9294463
负责人:
ANDREA GAMBOTTO
金额:
$19.33万
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:
2017-09-04 至 2019-08-31
关键词:
AdenovirusesAdjuvantAmericasAnimalsAntigensAntiviral AgentsArthropodsAttentionBrazilClinicalCountryCulicidaeCyclic AMPDengueDevelopmentDimerizationDisease OutbreaksEmergency SituationEnvironmentEvaluationFamilyFlavivirusGenesGoalsGuillain-Barré SyndromeHumanHumoral ImmunitiesHygieneIgG1Immune responseImmunityImmunizationImmunohistochemistryInfectionJapanese EncephalitisLiteratureMeasuresMicrocephalyModelingMonitorMusNamesNewborn InfantNucleotidesOrganPassive ImmunityPathway interactionsPeriodicityPoly I-CRecombinantsRegimenReportingSubunit VaccinesSystemTestingTitrationsVaccinatedVaccinesVirusVirus ReplicationVirus SheddingWest Nile virusWorld Health OrganizationYellow FeverZika VirusZika virus vaccinebasedimerefficacy testingextracellularimmunogenicityin vivointraperitonealmonomernervous system disorderneutralizing antibodypre-clinicalpregnantreceptor bindingrecombinant virusresearch clinical testingresponsesocioeconomicssucklingvaccine candidatevaccine efficacyvaccine trialvectorvector-based vaccinevirus envelope
中文摘要
摘要
英文摘要
Abstract
Since first detected in the Americas in May 2015 after rapidly spreading from Brazil, the mosquito-borne Zika
virus (ZIKV) has attracted global attention. The ZIKV outbreak in Brazil has also been associated with a
significant rise in the number of babies born with microcephaly and neurological disorders such as Guillain-
Barré syndrome and has been declared a “global emergency” by the World Health Organization. Zika virus is
related to dengue, yellow fever, Japanese encephalitis, and West Nile viruses, all of which are arthropod-borne
flaviviruses. Building on successful flavivirus vaccine approaches reported in the literature as an initial attempt
to develop a Zika virus vaccine, we have generated a panel of recombinant Zika virus subunit vaccines based
on the extracellular portion of the ZIKV envelope gene or the EDIII domain of the ZIKV envelope gene. The
EDIII loop of the flavivirus envelope gene is the receptor-binding domain and has been shown to be the most
promising target for an antiviral neutralizing immunity. Both these antigens (E and EDIII) were generated as
monomers (ZIKV-rE and ZIKV-rEDIII), as dimers in fusion with the fc portion of the human IgG1 (ZIKV-rEhIg
and ZIKV-rEDIIIhIg), and as trimers in fusion with the T4 fibritin foldon trimerization domain (ZIKV-rEfl and
ZIKV-rEDIIIfl). In the preliminary studies presented here, we tested the immunogenicity of trimeric ZIKV-rEfl
and ZIKV-rEDIIIfl delivered transcutaneously using dissoluble microneedle array (MNA) delivery system into
C57BL6 mice. The choice of the MNA-based antigen delivery system is justified because its efficacy and it is
simple and easily adaptable to use in low hygiene and pure socio-economic environment. We compared their
immunogenicity with the immunogenicity of the same antigens delivered with adenovirus 5-based vaccine
vector. We now are proposing extending the testing to all six ZIKV recombinant subunit vaccines generated.
The immunogenicity of these six subunit vaccines, named ZIKV-rE, ZIKV-rEDIII, ZIKV-rEhIg, ZIKV-rEDIIIhIg,
ZIKV-rEfl, and ZIKV-rEDIIIfl, delivered via MNA, will be compared in C57B6 mice. Once the best performing
ZIKV subunit vaccine is selected, the beneficial effect of adjuvant will be evaluated. Ultimately, we will test the
efficacy of the selected subunit vaccine in a ZIKV surrogate animal challenge model. We hypothesize that
administration of ZIKV subunit vaccines in a prime/boost regimen will elicit ZIKV-specific immunity that will lead
to the effective immunization of pregnant mice with passage of passive immunity to newborns, which will be
protected by ZIKV challenge.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
U01 Proposal Transfer - 2021
-
批准号:10406767
-
项目类别:
-
资助金额:$325.08万
-
财政年份:2019
-
负责人:ANDREA GAMBOTTO
-
依托单位:
Pre-clinical evaluation of an adenoviral-based MERS-CoV vaccine
-
批准号:8839373
-
项目类别:
-
资助金额:$17.86万
-
财政年份:2015
-
负责人:ANDREA GAMBOTTO
-
依托单位:
Pre-clinical evaluation of an adenoviral-based MERS-CoV vaccine
-
批准号:9108846
-
项目类别:
-
资助金额:$20.3万
-
财政年份:2015
-
负责人:ANDREA GAMBOTTO
-
依托单位:
Adenoviral-based vaccine platform to overcome neutralizing immunity
-
批准号:7777925
-
项目类别:
-
资助金额:$18.94万
-
财政年份:2010
-
负责人:ANDREA GAMBOTTO
-
依托单位:
Adenoviral-based vaccine platform to overcome neutralizing immunity
-
批准号:8070415
-
项目类别:
-
资助金额:$22.5万
-
财政年份:2010
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE FACILITY
-
批准号:8181037
-
项目类别:
-
资助金额:$6.13万
-
财政年份:2010
-
负责人:ANDREA GAMBOTTO
-
依托单位:
A Preventative Adenoviral-Based H5N1 Influenza Vaccine
-
批准号:7077267
-
项目类别:
-
资助金额:$96.24万
-
财政年份:2006
-
负责人:ANDREA GAMBOTTO
-
依托单位:
A Preventative Adenoviral-Based H5N1 Influenza Vaccine
-
批准号:7266987
-
项目类别:
-
资助金额:$24.36万
-
财政年份:2006
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE
-
批准号:7127020
-
项目类别:
-
资助金额:$10.13万
-
财政年份:2005
-
负责人:ANDREA GAMBOTTO
-
依托单位:
Preclinical Vector Core
-
批准号:7144460
-
项目类别:
-
资助金额:$71.21万
-
财政年份:2005
-
负责人:ANDREA GAMBOTTO
-
依托单位:
Uncoventional vectors for codon-optimized HIV antigens
-
批准号:6554007
-
项目类别:
-
资助金额:$22.41万
-
财政年份:2002
-
负责人:ANDREA GAMBOTTO
-
依托单位:
Uncoventional vectors for codon-optimized HIV antigens
-
批准号:6656339
-
项目类别:
-
资助金额:$22.34万
-
财政年份:2002
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE FACILITY
-
批准号:8705417
-
项目类别:
-
资助金额:$7.69万
-
财政年份:--
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE
-
批准号:7788812
-
项目类别:
-
资助金额:$9.54万
-
财政年份:--
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE
-
批准号:7596854
-
项目类别:
-
资助金额:$10.29万
-
财政年份:--
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE
-
批准号:7556959
-
项目类别:
-
资助金额:$10.05万
-
财政年份:--
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE
-
批准号:7556953
-
项目类别:
-
资助金额:$10.43万
-
财政年份:--
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE FACILITY
-
批准号:8382689
-
项目类别:
-
资助金额:$13.54万
-
财政年份:--
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE FACILITY
-
批准号:8307438
-
项目类别:
-
资助金额:$6.12万
-
财政年份:--
-
负责人:ANDREA GAMBOTTO
-
依托单位:
VECTOR CORE FACILITY
-
批准号:8519348
-
项目类别:
-
资助金额:$11.63万
-
财政年份:--
-
负责人:ANDREA GAMBOTTO
-
依托单位:
海外基金