Globally Appropriate Genome Reduced Killed Whole Bacterial HIV Vaccines
全球适用的基因组减少灭活全细菌 HIV 疫苗
基本信息
- 批准号:10672822
- 负责人:
- 金额:$ 56.53万
- 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:2023-03-13 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAdjuvantAnimal ModelAntibodiesAntibody Binding SitesAntibody FormationAntigensBacteriaBacterial VaccinesBindingBinding SitesBiological AssayBiomedical EngineeringBiomedical ResearchCellsCellular ImmunityChimeric ProteinsClinicalCold ChainsCombined VaccinesConsensusCoronavirusCryopreservationDNADNA biosynthesisDataDevelopmentDiseaseDoseEngineeringEnzyme-Linked Immunosorbent AssayEpidemicEscherichia coliEscherichia coli VaccinesExhibitsFamily suidaeFundingFutureGenomeGoalsHIVHIV AntigensHIV vaccineHIV-1HIV-1 vaccineHandHumanImmune responseImmunizeInactivated VaccinesIndustrializationInternationalKnowledgeLettersManufacturerMedicalMembraneModelingMonitorMonoclonal AntibodiesMusPeptide VaccinesPeptidesPhasePlasmidsPositioning AttributePreventive vaccineProductionProteinsRecombinantsRecording of previous eventsResearchRouteSafetyStructureStudy modelsSurfaceSystemT cell responseTechnology TransferTestingTrainingTranslatingVaccinatedVaccinationVaccine AntigenVaccine ProductionVaccinesViral AntigensViral Envelope ProteinsViral Fusion ProteinsVirusVirus DiseasesWhole Cell VaccineWorkantigen-specific T cellscell mediated immune responseclinical efficacycostdesignearly phase clinical trialforgivenesshigh rewardhigh riskimmunogenicityimprovedin vivo evaluationinnovationmanufacturing capabilitiesmeetingsmonomermouse modelneutralizing antibodyneutralizing monoclonal antibodiesnonhuman primatenovelnovel strategiesnovel vaccinesporcine epidemic diarrhea virusprophylacticresponsesafety assessmentskillssuccesssynthetic biologyvaccine candidatevaccine developmentvaccine immunogenicityvaccine platformvaccine response
项目摘要
A broad consensus regarding HIV vaccine development calls for engineering antigens that elicit production
of antibodies like the known Broadly Neutralizing (BN) Monoclonal Antibodies (MAbs). Two Env BN MAb
binding sites, the Membrane Proximal External Region (MPER) and Fusion Peptide (FP), are attractive targets
because they are linear peptides. We developed a new, low cost, globally appropriate vaccine platform: Killed
Whole Cell (KWC) Genome-Reduced E. coli (grEc), with vaccine antigens expressed on bacterial surfaces
using Gram- autotransporters. Using synthetic biology, testable vaccine candidates can be made in ~3 wks for
~$50 each. Vaccines made with the platform will cost ~$1/dose, can be produced in existing factories globally,
and have forgiving cold chain requirements. We made coronavirus FP vaccines using the KWC grEc platform
and showed clinical efficacy in an animal model. We propose to make KWC grEc HIV vaccines targeting
MPER and FP. Our preliminary data show that we can express HIV MPER and FP Ags with this approach and
elicit HIV neutralizing sera in mice using an MPER-derived Ag. We hypothesize that the KWC grEc platform,
targeting MPER and FP, will yield safe, effective, low cost, globally appropriate HIV vaccines.
In PHASE 1, Aim 1, we will synthesize DNAs encoding MPER and FP Ags, employing bioengineering
strategies to enhance Ag exposure and antigenicity. We will clone these DNAs into our expression plasmid and
transform into grEc to make KWC candidate vaccines. Using highly neutralizing and relatively non-neutralizing
MAbs, we will test candidate vaccines, selecting those that show the best difference in binding neutralizing vs.
less neutralizing MAbs for in vivo testing. In Aim 2, we will vaccinate mice to assess vaccine immunogenicity,
comparing the different candidate vaccines, alone and in combination, to identify the best vaccines and
dose/route/adjuvant using ELISAs, ELIspot assays, and PhenoSense neutralization assays against a
representative panel of viruses.
Decision Gate to progress to Phase 2: Production of a single or combination vaccine that elicits sera in
vaccinated mice yielding an IC50 >100 in the PhenoSense neutralization assay for ≥75% of mice immunized,
for ≥75% of HIV-1 Env reference strains, while sera from control immunized mice (mice immunized with
bacteria not expressing viral antigen) show no neutralization above baseline control.
In PHASE 2 we will, in Aim 3, conduct a non-human primate (NHP) model study to assess the safety,
immunogenicity, and ability to elicit a neutralizing Ab response by the vaccines. We expect that our vaccines
will induce specific HIV Ag-binding Abs, HIV antigen-specific T cell responses, and BN neutralizing Ab
responses in NHP, implying that the vaccine will be safe and effective in humans. KWC vaccines have a long
history, are inexpensive to make, and can be produced globally in existing facilities, we anticipate that our work
can be quickly translated into safe and effective, inexpensive, globally appropriate, prophylactic HIV vaccines.
关于艾滋病毒疫苗开发的广泛共识要求设计抗原以诱导生产
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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Steven L. Zeichner其他文献
Steven L. Zeichner的其他文献
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{{ truncateString('Steven L. Zeichner', 18)}}的其他基金
Pilot Study of Rectal Microbial Biomarkers for Appendicitis Diagnosis
用于诊断阑尾炎的直肠微生物生物标志物的初步研究
- 批准号:
9064769 - 财政年份:2015
- 资助金额:
$ 56.53万 - 项目类别:
Development of an in vivo screening technology for cancer vaccine immunogens
癌症疫苗免疫原体内筛选技术的开发
- 批准号:
8508685 - 财政年份:2011
- 资助金额:
$ 56.53万 - 项目类别:
Development of an in vivo screening technology for cancer vaccine immunogens
癌症疫苗免疫原体内筛选技术的开发
- 批准号:
8304214 - 财政年份:2011
- 资助金额:
$ 56.53万 - 项目类别:
Development of an in vivo screening technology for cancer vaccine immunogens
癌症疫苗免疫原体内筛选技术的开发
- 批准号:
8080672 - 财政年份:2011
- 资助金额:
$ 56.53万 - 项目类别:
WIRB - AN OPEN-LABEL, MULTIPLE-DOSE, CROSS-OVER STUDY TO EVALUATE: HIV
WIRB - 一项开放标签、多剂量、交叉研究来评估:HIV
- 批准号:
8167327 - 财政年份:2010
- 资助金额:
$ 56.53万 - 项目类别:
IMPAACT P1066: A PHASE I/II MULTICENTER, OPEN-LABEL, NONCOMPARATIVE STUDY OF
IMPAACT P1066:I/II 期多中心、开放标签、非比较研究
- 批准号:
8167353 - 财政年份:2010
- 资助金额:
$ 56.53万 - 项目类别:
PACTG P1047 SAFETY AND IMMUNOGENICITY OF QUADRIVALENT HUMAN PAPILLOMA VIRUS
PACTG P1047 四价人乳头瘤病毒的安全性和免疫原性
- 批准号:
8167345 - 财政年份:2010
- 资助金额:
$ 56.53万 - 项目类别:
PACTG P1047 SAFETY AND IMMUNOGENICITY OF QUADRIVALENT HUMAN PAPILLOMA VIRUS
PACTG P1047 四价人乳头瘤病毒的安全性和免疫原性
- 批准号:
7951109 - 财政年份:2008
- 资助金额:
$ 56.53万 - 项目类别:
IMPAACT P1066: A PHASE I/II MULTICENTER, OPEN-LABEL, NONCOMPARATIVE STUDY OF
IMPAACT P1066:I/II 期多中心、开放标签、非比较研究
- 批准号:
7951122 - 财政年份:2008
- 资助金额:
$ 56.53万 - 项目类别:
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