Biomaterial Strategies for Modulating the Immune Response
调节免疫反应的生物材料策略
基本信息
- 批准号:10232052
- 负责人:
- 金额:$ 10.67万
- 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:2020-08-10 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:3D PrintAddressAdjuvantAluminum HydroxideAnatomyAntibodiesAntibody FormationAntigensAreaB-LymphocytesBiocompatible MaterialsBiological PhenomenaCause of DeathCessation of lifeChemistryChildClinicalCommunicable DiseasesComplexDendritic CellsDermisDevelopmentDevicesDiseaseDoseDropoutDropsEconomicsElementsEmulsionsEngineeringEnvironmentEnvironmental Risk FactorEvaluationExhibitsExposure toFormulationGlycolatesHealth Care CostsHigh PrevalenceHuman PapillomavirusHydration statusHydrogelsImmune responseImmunityImmunizationImmunization ScheduleIn SituIndividualInfantInjectionsKineticsLogisticsMalaria VaccinesMalignant neoplasm of cervix uteriMechanicsMediatingMeningitisMethodsMolecular ConformationNaturePhysiologic pulsePolymersProceduresProcessPropertyRegimenResearchResolutionResourcesRiskSelf AdministrationShapesSiteSkinSolventsStructureSubunit VaccinesSurfaceTechnologyTimeUnited StatesVaccinationVaccinesWorkWorld Health Organizationbaseclinically relevantcontrolled releasecostdensityevaporationimmunogenicimmunogenicityimmunomodulatory strategyimprovedin vivolymph nodesnanoparticleneutralizing antibodynovelpain reductionparticlepolymerizationpreclinical studypreventprogramsresidenceseroconversionsuccesstooltwo-photonvaccine deliveryvaccine developmentvaccine distributionvaccine responsevaccine trial
项目摘要
PROJECT SUMMARY/ABSTRACT
Despite the enormous success of the World Health Organization's Expanded Programme on Immunization,
which has saved millions of lives over the past 44 years, infectious disease remains the second leading cause
of death worldwide.1-4 Of the 15 million deaths that occur each year, 10% are vaccine-preventable, yet continue
to occur due to the logistical challenges associated with administering multiple injections over the course of
months in low-resource settings.5 The remaining 90% of deaths cannot be prevented with existing vaccines and
will likely require the development of highly immunogenic vaccines against key disease targets.6,7 For example,
RTS,S/AS01 (MosquirixTM), the only clinically-approved malaria vaccine, is effective in just 26% of young children
after 3 doses and 39% of children after 4 doses.8 Although additional doses may further improve seroconversion
rates, there are limits to economic and societal tolerance for additional doses.9 Instead, strategies that enhance
antigen immunogenicity may be able to: (1) achieve similar levels of seroconversion after fewer doses, (2)
improve seroconversion rates after the same number of doses, and/or (3) enable the use of subunit vaccines
that are typically safer and more stable, but inherently less immunogenic.10 In addition to addressing a clear
clinical need in the developing world, this strategy is also relevant for the developed world, especially for human
papillomavirus (HPV) and meningitis vaccines, which require multiple doses, but are subject to low initial
compliance (one-dose coverage of 66% and 85% in the U.S., respectively) and high drop-out rates (25% and
52% of individuals that receive one dose do not receive a second).11-13 My postdoctoral research has primarily
focused on the development of a single-injection vaccination platform that uses biodegradable microparticles to
release antigen in discrete pulses that mimic multiple injections. This proposal builds off of my previous work
and aims to not just replicate the immunogenicity of multi-injection immunization regimens, but enhance vaccine
immunogenicity using three timed or targeted vaccine delivery strategies. The first approach will develop a
vaccine delivery platform that uses ultrahigh resolution 3D printing to fabricate surface-eroding microparticles
that exhibit well-controlled release kinetics and protect antigen from harmful environmental factor. Because
optimal vaccine release kinetics have yet to not been identified,14 these devices will also be used to determine
favorable release profiles. The second approach will create dissolvable microneedle patches for the intradermal
delivery of controlled release vaccines. By leveraging the high concentration of dendritic cells in the skin and
benefits of delayed release, these formulations may be able to enhance vaccine immunogenicity while offering
other advantages such as improved antigen stability, reduced pain, and the potential for self-administration. The
third strategy presented in this proposal will explore the use of in situ-forming hydrogels that self-assemble in
the lymph node and release vaccine over time to prolong antigen residence time and exposure to naïve B cells.
项目总结/摘要
尽管世界卫生组织扩大免疫方案取得了巨大成功,
在过去的44年里,它拯救了数百万人的生命,但传染病仍然是第二大死因。
1 -4在每年发生的1500万例死亡中,10%是疫苗可预防的,但仍在继续
由于与在治疗过程中给予多次注射相关的后勤挑战,
5其余90%的死亡无法通过现有疫苗预防,
可能需要开发针对关键疾病目标的高免疫原性疫苗。6,7例如,
RTS,S/AS 01(MosquirixTM)是唯一获得临床批准的疟疾疫苗,仅对26%的幼儿有效
39%的儿童在4剂后发生。8尽管额外剂量可能进一步改善血清转化
然而,由于剂量增加,经济和社会对额外剂量的容忍是有限的。
抗原免疫原性可能能够:(1)在较少剂量后达到相似的血清转化水平,(2)
在相同剂量后提高血清转化率,和/或(3)能够使用亚单位疫苗
通常更安全和更稳定,但本质上免疫原性较低。
虽然发展中国家的临床需求,但该策略也适用于发达国家,特别是人类
乳头瘤病毒(HPV)和脑膜炎疫苗,需要多次接种,但初始接种率低,
依从性(在美国,一剂覆盖率为66%和85%,辍学率高(25%,
52%的人接受了一次剂量,没有接受第二次)。
专注于开发单次注射疫苗平台,该平台使用可生物降解的微粒,
以模拟多次注射的离散脉冲释放抗原。这个建议建立在我以前的工作基础上
目的不仅是复制多次注射免疫方案的免疫原性,
使用三种定时或靶向疫苗递送策略的免疫原性。第一种方法将开发一个
一种疫苗输送平台,使用100分辨率3D打印来制造表面侵蚀微粒
其表现出良好受控释放动力学并保护抗原免受有害环境因素的影响。因为
最佳的疫苗释放动力学尚未确定,14这些装置也将用于确定
有利的释放曲线。第二种方法将为皮内注射创造可溶解的微针贴片。
控制释放疫苗。通过利用皮肤中高浓度的树突细胞,
由于延迟释放的益处,这些制剂可能能够增强疫苗免疫原性,同时提供
其它优点如提高的抗原稳定性、减少的疼痛和自我给药的潜力。的
第三个战略提出了这项建议将探讨使用原位形成水凝胶,自组装,
淋巴结并随时间释放疫苗以延长抗原停留时间和暴露于幼稚B细胞。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kevin James McHugh其他文献
Kevin James McHugh的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kevin James McHugh', 18)}}的其他基金
Research Supplement to Promote Diversity: Carlos Torres (R03EB031495 Parent Award)
促进多样性的研究补充:Carlos Torres(R03EB031495 家长奖)
- 批准号:
10592146 - 财政年份:2022
- 资助金额:
$ 10.67万 - 项目类别:
Research Supplement to Promote Diversity: Belvi Bwela (R03EB031495 Parent Award)
促进多样性的研究补充:Belvi Bwela(R03EB031495 家长奖)
- 批准号:
10592142 - 财政年份:2022
- 资助金额:
$ 10.67万 - 项目类别:
Electrosprayed Core-Shell Microparticles as a Pulsatile Vaccine Delivery Platform
电喷雾核壳微粒作为脉冲疫苗输送平台
- 批准号:
10195135 - 财政年份:2021
- 资助金额:
$ 10.67万 - 项目类别:
Solvent Evaporator Equipment Supplement to R35GM143101
R35GM143101 溶剂蒸发器设备补充
- 批准号:
10799251 - 财政年份:2021
- 资助金额:
$ 10.67万 - 项目类别:
Next-Generation Parenteral Drug Delivery Systems for Controlling Pharmacokinetics
用于控制药代动力学的下一代肠外给药系统
- 批准号:
10277139 - 财政年份:2021
- 资助金额:
$ 10.67万 - 项目类别:
Electrosprayed Core-Shell Microparticles as a Pulsatile Vaccine Delivery Platform
电喷雾核壳微粒作为脉冲疫苗输送平台
- 批准号:
10372138 - 财政年份:2021
- 资助金额:
$ 10.67万 - 项目类别:
Next-Generation Parenteral Drug Delivery Systems for Controlling Pharmacokinetics
用于控制药代动力学的下一代肠外给药系统
- 批准号:
10890222 - 财政年份:2021
- 资助金额:
$ 10.67万 - 项目类别:
Research Supplement to Promote Diversity: Mei-Li Laracuente (1R35GM143101 Parent Award)
促进多样性的研究补充:Mei-Li Laracuente(1R35GM143101家长奖)
- 批准号:
10631614 - 财政年份:2021
- 资助金额:
$ 10.67万 - 项目类别:
Next-Generation Parenteral Drug Delivery Systems for Controlling Pharmacokinetics
用于控制药代动力学的下一代肠外给药系统
- 批准号:
10667652 - 财政年份:2021
- 资助金额:
$ 10.67万 - 项目类别:
Next-Generation Parenteral Drug Delivery Systems for Controlling Pharmacokinetics
用于控制药代动力学的下一代肠外给药系统
- 批准号:
10488240 - 财政年份:2021
- 资助金额:
$ 10.67万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Research Grant