Eliciting tyrosine-sulfated neutralizing antibodies recognizing the Env apex
引发识别 Env 顶点的酪氨酸硫酸化中和抗体
基本信息
- 批准号:10013483
- 负责人:
- 金额:$ 23.13万
- 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:2020-03-06 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:AbbreviationsAffinityAntibodiesAntibody DiversityAntigen TargetingAntigensB-LymphocytesBindingBinding SitesCharacteristicsDataEngineeringEpitopesFoundationsGenesGlycoproteinsGoalsHIVHIV-1HIV-1 vaccineHemocyaninHumanImmune SeraImmunizationImmunizeImmunoglobulin Somatic HypermutationIndividualKeyhole Limpet HemocyaninKnowledgeLightModelingMutationPolysaccharidesPopulationPropertyProtein FamilyRattusReceptors, Antigen, B-CellSideSulfateTestingTransferaseVaccinesWistar RatsWorkbasecomplementarity-determining region 3crosslinkdesigndisulfide bondinterestnanoparticleneutralizing antibodynonhuman primatenovel strategiespreventprotein-tyrosine sulfotransferasescaffoldsuccesstransmission processtyrosine O-sulfate
项目摘要
PROJECT SUMMARY
An effective HIV-1 remains an important but elusive goal. One promising approach to such a vaccine
uses sequential immunization to guide B-cell receptor (BCR) maturation. To do so, one first amplifies
immature unmutated precursors of a particular class of broadly neutralizing antibodies (bNAbs). These
precursor BCR are then shepherded to recognize HIV-1 envelope glycoprotein (Env) using increasingly
native Env antigens. Sequential immunization strategies for both VRC01- and V3-glycan-classes of
bNAbs are being developed. Here we establish the foundations for using the same general strategy to
elicit V2-glycan/apex antibodies. Apex bNAbs have properties that both complicate such an approach
but ultimately make success more likely. Specifically these bNAbs bind Env largely through their long,
acidic and tyrosine-sulfated heavy-chain CDR3 region. Thus there is less need for extensive somatic
hypermutaion characteristic of V3-glycan and VRC01-class bNAbs. However, apart from their long
sulfated CDR3 regions, apex bNAbs have few distinguishing features. Here we show that we can elicit
antibodies in rats with long tyrosine-sulfated CDR3 regions using anti-sulfotyrosine antibodies as
antigens. We propose to optimize this approach and use it in concert with oligomeric forms of Env trimers
to elicit anti-apex antibodies. These studies will develop a potentially easier approach to generating
broad and potent anti-HIV-1 antisera.
项目摘要
有效的HIV-1仍然是一个重要但难以实现的目标。一种有希望的疫苗方法
使用顺序免疫来引导B细胞受体(BCR)成熟。要做到这一点,首先要放大
特定类别的广泛中和抗体(bNAb)的未成熟的未突变的前体。这些
前体BCR然后被引导识别HIV-1包膜糖蛋白(Env),
天然Env抗原。针对VRC 01-和V3-聚糖类的顺序免疫策略
BNAB正在开发中。在这里,我们建立了使用相同的一般策略的基础,
引发V2-聚糖/顶点抗体。Apex bNAb具有使这种方法复杂化的性质
但最终使成功更有可能。具体地说,这些bNAb主要通过它们的长,
酸性和酪氨酸硫酸化重链CDR 3区。因此,不太需要广泛的体细胞
V3-聚糖和VRC 01-类bNAb超突变特征。然而,除了他们的长期
在硫酸化的CDR 3区中,顶端bNAb具有很少的区别特征。这里我们展示了我们可以引出
使用抗磺基酪氨酸抗体,
抗原我们建议优化这种方法,并将其与Env三聚体的寡聚形式一起使用
来引发抗顶点抗体这些研究将开发一种潜在的更容易的方法来产生
广泛和有效的抗HIV-1抗血清。
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)
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Michael R. Farzan其他文献
Michael R. Farzan的其他文献
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{{ truncateString('Michael R. Farzan', 18)}}的其他基金
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Safe, CRISPR/Cas-free B cell editing for therapeutic applications
用于治疗应用的安全、无 CRISPR/Cas 的 B 细胞编辑
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10573644 - 财政年份:2022
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Improving mRNA vaccines with extracellular vesicle-associated immunogens
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10850617 - 财政年份:2022
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10844837 - 财政年份:2022
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$ 23.13万 - 项目类别:
Therapeutic Use of an Enhanced Form of CD4-Ig
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- 批准号:
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- 资助金额:
$ 23.13万 - 项目类别:
Therapeutic use of an enhanced form of CD4-Ig
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10851165 - 财政年份:2020
- 资助金额:
$ 23.13万 - 项目类别:
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