AAV Vectored Delivery of Broadly Neutralizing Antibodies with Optimal Innate Functionality Against HIV
AAV 载体递送具有针对 HIV 的最佳先天功能的广泛中和抗体
基本信息
- 批准号:10762553
- 负责人:
- 金额:$ 79.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-15 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AIDS preventionAddressAnimal ExperimentsAnimal ModelAntibodiesAntibody-mediated protectionAutomobile DrivingBLT miceBindingBiological AssayBone MarrowCell physiologyCell surfaceCellsClinical TrialsDataDependovirusDoctor of PhilosophyEffectivenessEffector CellEngineeringEpitopesExhibitsFutureGene TransferGrantHIVHIV InfectionsHIV therapyHumanImmuneImmune systemImmunityImmunoglobulin FragmentsImmunoglobulin GIn VitroIndividualInfectionLiverMacrophageMeasuresMediatingMembrane FusionModelingMutationNatural ImmunityNatural Killer CellsNeutralization TestsNeutralizing antibody assayPatientsPatternPhagocytosisPopulationPreventionPrincipal InvestigatorResearchRoleSerumSideSpecificitySurfaceTechnologyTestingThymus GlandVaginaViralViremiaWorkadeno-associated viral vectorantibody engineeringantibody-dependent cell cytotoxicityantibody-dependent cellular phagocytosiscomparative efficacydelivery vehiclehumanized mouseimmunoengineeringimmunoprophylaxisin vitro Assayin vivoinnate immune functioninnate immune mechanismsmedical schoolsneutralizing antibodynext generationnovelpreventprofessorprotective efficacyreceptorreceptor bindingtransmission processvaginal transmissionvector
项目摘要
Project Summary / Abstract
This proposal describes the framework of an R01 grant for Alejandro Balazs, PhD. Dr. Balazs is
currently an assistant professor at Harvard Medical School working as a principal investigator at the Ragon
Institute of MGH, MIT & Harvard. Dr. Balazs’ research is focused on engineering the immune system via gene
transfer as a novel means of creating protection against HIV. Broadly neutralizing antibodies (bNAbs) against
human immunodeficiency virus (HIV) show great promise in HIV prevention and therapy as they potently
neutralize a significant breadth of globally circulating HIV strains. A number of animal experiments and clinical
trials have demonstrated the ability of bNAbs to confer protection from viral challenge and reduce viremia of
established infections. BNAbs can inhibit HIV infection by blocking viral attachment or membrane fusion;
however, recent work suggests that the fragment crystallizable (Fc) region of antibodies may also contribute
significantly to bNAb-mediated HIV inhibition through interactions with innate immunity. This proposal seeks to
use in vitro cell-based assays to determine the extent to which next-generation HIV bNAbs engage effector
functions, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular
phagocytosis (ADCP). This proposal will modify the Vectored ImmunoProphylaxis technology pioneered by Dr.
Balazs to generate sustained expression of antibodies harboring precise Fc-region mutations previously
demonstrated to enhance or abrogate, Fc-receptor interactions. By manipulating the specificity and
concentration of these antibodies, this study will define the rules governing Fc-receptor engagement that apply
to prevention of HIV acquisition. Furthermore, it seeks to determine the potential for Fc-enhanced antibodies to
increase the potency of bNAb protection against HIV transmission. Finally, this proposal will manipulate the
immune system of humanized mice as a means of dissecting and precisely quantifying the contribution of
specific immune cells to prevention of HIV transmission. Together, this work will reveal optimal epitope targets
and innate immune mechanisms to produce next-generation AAV vectors encoding bNAbs with enhanced
innate immune function to prevent HIV transmission.
项目摘要/摘要
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
mRNA-based monkeypox virus vaccine prevents disease in non-human primates.
基于 mRNA 的猴痘病毒疫苗可预防非人类灵长类动物的疾病。
- DOI:10.1016/j.cell.2024.02.011
- 发表时间:2024
- 期刊:
- 影响因子:64.5
- 作者:Nitido,AdamN;Balazs,AlejandroB
- 通讯作者:Balazs,AlejandroB
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Alejandro Benjamin Balazs其他文献
Alejandro Benjamin Balazs的其他文献
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{{ truncateString('Alejandro Benjamin Balazs', 18)}}的其他基金
Development of Vectored ImmunoProphylaxis as a strategy against HIV
开发载体免疫预防作为抗 HIV 策略
- 批准号:
8411105 - 财政年份:2014
- 资助金额:
$ 79.69万 - 项目类别:
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