Next Generation Multipurpose Prevention Technology: An Intravaginal Ring for HIV Prevention and Nonhormonal Contraception
下一代多用途预防技术:用于艾滋病毒预防和非激素避孕的阴道环
基本信息
- 批准号:10588268
- 负责人:
- 金额:$ 74.67万
- 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:2020-05-05 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AIDS preventionAdherenceAffinityAfricanAgglutinationAnimal ModelAnti-Retroviral AgentsAntibodiesAntigen TargetingAutomobile DrivingBehavior monitoringBiological AssayBiologyBlocking AntibodiesCellsChemistryClinicalClinical TrialsCollaborationsComplementContraceptive AgentsContraceptive methodsDataDevelopmentDoseDrug CombinationsDrug Delivery SystemsDrug KineticsDrug StabilityEngineeringEpidemicFamily PlanningFutureGoalsHIVHIV InfectionsHormonesHourHumanHybridsImmunoglobulin GIn VitroIndividualInfectionKineticsKnowledgeLeadMacacaMacaca nemestrinaMeasuresMethodsModelingMonitorMonoclonal AntibodiesMucous body substanceOralPersonsPharmaceutical PreparationsPharmacologyPre-Clinical ModelPregnancyPreparationPreventionProcessPropertyPublic HealthRegimenResearchResearch PersonnelRiskSafetySheepSperm AgglutinationSwimmingTechnologyTemperatureTemperature SenseVaginaVaginal RingWomanYeastsarmbiocompatible polymerclinical efficacycontraceptive efficacycostcost effectivedesigneggfabricationglobal healthhealth organizationhuman malein vivoinfection rateinnovationinterestlead candidatemultiple omicsnanomolarnext generationnonhuman primatenovelpharmacokinetics and pharmacodynamicspre-clinicalpre-exposure prophylaxispreventprototypereproductive tractresponsesafety assessmentsexsimian human immunodeficiency virussmall moleculesperm cellsuccesstransmission processunintended pregnancyuptakevaginal microbiome
项目摘要
ABSTRACT
New HIV infection rates far outpace the targets set by global health organizations, despite important progress
in curbing the progression of the epidemic. In 2017, an estimated 1.8 million people became newly HIV
infected globally. New HIV pre-exposure prophylaxis (PrEP) strategies are needed urgently to curb this
alarming situation, particularly in young sub-Saharan African women who are disproportionately at risk. A high
proportion of women at risk of becoming HIV-infected also are interested in family planning, suggesting that a
dual-purpose product providing HIV prevention and contraception would significantly increase the likelihood of
higher uptake relative to single-purpose products, since unsurprisingly, women do not self-identify as being at
risk of HIV, but do so identify for pregnancy. Many women are averse to exogenous hormones and would
strongly prefer a nonhormonal method, and one that does not require use immediately before or after sex. Our
application integrates two leading innovations in developing a next generation multi-purpose technology (MPT)
intravaginal ring (IVR): (1) developing a novel, nonhormonal contraceptive agent based on a multivalent
monoclonal antibody (mAb) that blocks sperm from swimming through mucus and accessing the egg; and (2)
formulating the mAb contraceptive with antiretroviral (ARV) agents with demonstrated clinical efficacy in
preventing HIV in a behavior-monitoring IVR. We have recently engineered a unique IgG-based multivalent
mAb with 10 Fab arms against CD52g, a validated antigen target for contraception that is found only on cells in
the human male genital tract. This molecule, even at sub-nanomolar concentrations, effectively agglutinates
>99% of sperm within seconds, thus offering potentially potent yet cost-effective contraception. To complement
this novel agent, our team has developed an innovative IVR platform that delivers drug combinations including
small molecule drugs and mAbs. A low-cost module has been incorporated into the IVR to monitor temperature
as a surrogate measure of adherence. The MPT IVR will be formulated to provide long-term (30 days) dual
protection while evaluating adherence. In Aim 1, we will further enhance the mAb constructs against CD52g
through affinity maturation of anti-CD52g Fab using yeast-display, incorporate the optimized Fab into similar
multimeric mAb formats, and characterize their sperm agglutination potencies rigorously. In Aim 2, we will
formulate and evaluate in vitro human- and macaque-sized MPT IVRs to deliver our lead contraceptive mAb
candidate in combination with ARV drugs at target in vitro rates based on existing in vivo PK-PD data. We will
optimize and expand the adherence IVR design and evaluate prototypes in sheep. In Aim 3, we will assess the
pharmacokinetics and pharmacodynamics (safety and efficacy) of MPT IVR candidates in sheep and pigtailed
macaques. This project builds on an established collaboration of investigators and will advance our scientific
knowledge on the properties of sustained-release vaginal drug delivery in the context of HIV prevention and
contraception.
摘要
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Marc Michael Baum其他文献
Marc Michael Baum的其他文献
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{{ truncateString('Marc Michael Baum', 18)}}的其他基金
Sustained Release of Potent Antiviral Prodrugs for HIV Prevention
持续释放有效的抗病毒前药以预防艾滋病毒
- 批准号:
10617540 - 财政年份:2023
- 资助金额:
$ 74.67万 - 项目类别:
Systemic Sustained Release Delivery of Antiretroviral Agents for HIV Prevention
用于预防艾滋病毒的抗逆转录病毒药物的全身缓释递送
- 批准号:
10449318 - 财政年份:2021
- 资助金额:
$ 74.67万 - 项目类别:
Systemic Sustained Release Delivery of Antiretroviral Agents for HIV Prevention
抗逆转录病毒药物的全身缓释递送用于预防艾滋病毒
- 批准号:
10327138 - 财政年份:2021
- 资助金额:
$ 74.67万 - 项目类别:
Systemic Sustained Release Delivery of Antiretroviral Agents for HIV Prevention
用于预防艾滋病毒的抗逆转录病毒药物的全身缓释递送
- 批准号:
10654774 - 财政年份:2021
- 资助金额:
$ 74.67万 - 项目类别:
Next Generation Multipurpose Prevention Technology: An Intravaginal Ring for HIV Prevention and Nonhormonal Contraception
下一代多用途预防技术:用于艾滋病毒预防和非激素避孕的阴道环
- 批准号:
10158504 - 财政年份:2020
- 资助金额:
$ 74.67万 - 项目类别:
Next Generation Multipurpose Prevention Technology: An Intravaginal Ring for HIV Prevention and Nonhormonal Contraception
下一代多用途预防技术:用于艾滋病毒预防和非激素避孕的阴道环
- 批准号:
9926590 - 财政年份:2020
- 资助金额:
$ 74.67万 - 项目类别:
Next Generation Multipurpose Prevention Technology: An Intravaginal Ring for HIV Prevention and Nonhormonal Contraception
下一代多用途预防技术:用于艾滋病毒预防和非激素避孕的阴道环
- 批准号:
10359111 - 财政年份:2020
- 资助金额:
$ 74.67万 - 项目类别:
Systemic Sustained Release Delivery of Antiretroviral Agents for HIV Prevention
抗逆转录病毒药物的全身缓释递送用于预防艾滋病毒
- 批准号:
9089920 - 财政年份:2015
- 资助金额:
$ 74.67万 - 项目类别:
Systemic Sustained Release Delivery of Antiretroviral Agents for HIV Prevention
抗逆转录病毒药物的全身缓释递送用于预防艾滋病毒
- 批准号:
9277368 - 财政年份:2015
- 资助金额:
$ 74.67万 - 项目类别:
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