Messenger RNA Immunogens for initiation of protective HIV non-neutralizing antibodies
用于启动保护性 HIV 非中和抗体的信使 RNA 免疫原
基本信息
- 批准号:10355426
- 负责人:
- 金额:$ 387.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-01-11 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:ALVACAddressAlgorithmsAnimalsAntibodiesAntibody ResponseAntigensB-LymphocytesBindingCell LineageContractsDataEncapsulatedFormulationGoalsGrantHIVHIV Envelope Protein gp120HIV Vaccine Trials NetworkHIV-1HIV-1 vaccineHumanImmunizationInfectionInvestigational New Drug ApplicationLeadMacacaMacaca mulattaMediatingMessenger RNAMosaicismPhasePhase I Clinical TrialsProductionProteinsRNA vaccinationRegimenRiskT-LymphocyteT-Lymphocyte EpitopesTechnologyTestingTherapeuticToxic effectVaccinationVaccine DesignVaccinesWorkWritingaluminum sulfateantibody-dependent cellular phagocytosisdesignefficacy trialexpectationexperimental studyfirst-in-humanhomologous recombinationimmunogenicimprovedin silicoin vivolipid nanoparticlemanmeetingsmouse modelneutralizing antibodynew technologynovelphase I trialprogramsresponsesimian human immunodeficiency virustransmission processvaccine developmentvaccine efficacyvaccine strategyvaccine trial
项目摘要
While HIV-1 broadly neutralizing antibodies (bnAbs) provide potent protection from HIV-1, to date they have
been difficult to induce in the setting of vaccination. A second type of HIV-1 envelope (Env) antibodies that are
easy to induce are termed non-neutralizing antibodies (NNAbs) (because they are not bnAbs), or called
effector antibodies, because they mediate a myriad of potentially protective anti-HIV-1 effector mechanisms.
One of the 5 Phase IIb HIV-1 vaccine efficacy trials (ALVAC/AIDSVAX in RV144) showed an estimated
vaccine efficacy of 31%, with a correlate of decreased transmission risk of polyfunctional antibodies that
mediate FcR-anti-HIV-1 activities including C1 and V2-targeted ADCC. Currently there are two vaccine
efficacy trials ongoing to test the ability of an ALVAC-C, bivalent C/C gp120 boost (HVTN 702) and rAd26
prime, gp140 protein boost (HVTN 705) with hopes of inducing protective NNAbs. HVTN 702 has two wildtype
(WT) gp120 Envs as boosts, and HVTN 705 has one WT Env as boost. However, neither trial utilitize
strategies for inducing a breadth of NNAbs with boosting Env design. Thus, a key goal of current HIV-1
vaccine development is to develop the simplest and most effective vaccine that induces polyfunctional NNAbs
should either of the current efficacy trials fail to improve on RV144.
Our overall goals are 1) to develop an ADCC mosaic multivalent Env immunogen to follow an ALVAC-C
prime; and 2) to produce ADCC mosaic Env gp120s under current good manufacturing practices (CGMP)
conditions, perform toxicity studies, and prepare an investigational new drug application (IND) for testing in an
HVTN Phase I clinical trial in man.
Overall Specific Aim 1. Develop and produce a trivalent ADCC mosaic Env immunogen that can
follow an ALVAC-C prime and test them in the Animal Core in an ADCC mediating NNAb-unmutated
common ancestor (UCA) VH + VL mouse model and in a transmitted/founder (TF) tier 2, R5 SHIV
rhesus macaque study (RMs) (Drew Weissman, Project Lead; Barton Haynes, Co-I)
Overall Specific Aim 2. Produce CGMP trivalent ADCC mosaic mRNA gp120 immunogens. (Thomas
Denny Project Lead; Maureen Maughan, Project Co-I)
.
虽然HIV-1广泛中和抗体(bnAbs)提供了对HIV-1的有效保护,但迄今为止它们确实具有
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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Barton F. Haynes其他文献
Human thymic epithelium and T cell development: current issues and future directions.
人类胸腺上皮和 T 细胞发育:当前问题和未来方向。
- DOI:
- 发表时间:
1990 - 期刊:
- 影响因子:0
- 作者:
Barton F. Haynes - 通讯作者:
Barton F. Haynes
Mechanisms of corticosteroid action on lymphocyte subpopulations. IV. Effects of in vitro hydrocortisone on naturally occuring and mitogen-induced suppressor cells in man.
皮质类固醇对淋巴细胞亚群的作用机制。
- DOI:
- 发表时间:
1979 - 期刊:
- 影响因子:4.3
- 作者:
Barton F. Haynes;A. Fauci - 通讯作者:
A. Fauci
Phenotypic characterization of human cytolytic T lymphocytes in mixed lymphocyte culture
混合淋巴细胞培养物中人溶细胞性 T 淋巴细胞的表型特征
- DOI:
- 发表时间:
1981 - 期刊:
- 影响因子:15.3
- 作者:
A. Moretta;M. Mingari;Barton F. Haynes;R. Sékaly;L. Moretta;A. Fauci - 通讯作者:
A. Fauci
Early corneal findings in Cogan's syndrome.
科根综合征的早期角膜发现。
- DOI:
10.1016/s0161-6420(84)34215-4 - 发表时间:
1984 - 期刊:
- 影响因子:13.7
- 作者:
L. Michael Cobo;Barton F. Haynes - 通讯作者:
Barton F. Haynes
Human Erythrocyte Antigens: II. The <em>In(Lu)</em> Gene Regulates Expression of an Antigen on an 80-Kilodalton Protein of Human Erythrocytes
- DOI:
10.1182/blood.v64.3.599.599 - 发表时间:
1984-09-01 - 期刊:
- 影响因子:
- 作者:
Marilyn J. Telen;Thomas J. Palker;Barton F. Haynes - 通讯作者:
Barton F. Haynes
Barton F. Haynes的其他文献
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{{ truncateString('Barton F. Haynes', 18)}}的其他基金
Project 3: Nucleoside-modified mRNA-LNP vaccine platform
项目3:核苷修饰mRNA-LNP疫苗平台
- 批准号:
10842504 - 财政年份:2021
- 资助金额:
$ 387.82万 - 项目类别:
Project 3: Nucleoside-modified mRNA-LNP vaccine platform
项目3:核苷修饰mRNA-LNP疫苗平台
- 批准号:
10327525 - 财政年份:2021
- 资助金额:
$ 387.82万 - 项目类别:
Design and Development of a Pan-betacoronavirus Vaccine
泛β冠状病毒疫苗的设计与开发
- 批准号:
10842498 - 财政年份:2021
- 资助金额:
$ 387.82万 - 项目类别:
Design and Development of a Pan-betacoronavirus Vaccine
泛β冠状病毒疫苗的设计与开发
- 批准号:
10327519 - 财政年份:2021
- 资助金额:
$ 387.82万 - 项目类别:
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