Intranasal Vaccine Against Lyme Disease

莱姆病鼻内疫苗

• 批准号: 10491410
• 负责人: Maria Gomes-Solecki
• 金额: $ 98.85万
• 依托单位: IMMUNO TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-12 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491410
• 关键词: Adult; Affect; American; Animal Model; Antigens; Biological Assay; Borrelia burgdorferi; COVID-19; COVID-19 vaccine; Centers for Disease Control and Prevention (U.S.); Clinical Trials; Data; Development; Dose; Elderly; Epitopes; Genetic; Human; Immune response; Immunity; Immunization; Immunization Schedule; Immunize; Immunoglobulin G; Infection; Intranasal Administration; Investigational Drugs; Laboratories; Lead; Length; Longevity; Lyme Disease; Lyme Disease Vaccines; Methods; Modeling; Monkeys; Mus; Needles; New Drug Approvals; Nymph; OspA protein; OspA vaccine; Parainfluenza; Performance; Phase; Phase I Clinical Trials; Primates; Production; Research; Safety; Schedule; Seeds; Self Administration; Small Business Innovation Research Grant; Specific qualifier value; Technology; Ticks; TimeLine; Tissues; Trademark; Vaccination; Vaccines; Vector-transmitted infectious disease; Vero Cells; Viral Vector; aluminum sulfate; base; cell bank; commercialization; delivery vehicle; immunogenic; immunogenicity; nonhuman primate; novel; novel vaccines; pre-clinical assessment; preclinical study; prevent; response; subcutaneous; tick transmission; vaccination protocol; vaccine access; vaccine candidate; vaccine delivery; vaccine efficacy; vaccine hesitancy; vector-induced

ABSTRACT We propose to develop intranasal, parainfluenza 5 (PIV5) viral-vector delivered vaccines against human Lyme disease (LD) to be administered using a prime-boost schedule, for the US market. A recent new estimate of LD by the CDC places the new number at 476,000 annual cases, up from 329,000 in 2015 which strongly suggests that the number of Americans affected by this vector-borne disease is increasing. Currently, there is no human Lyme Disease vaccine available in the market. A prime-boost vaccination with an intranasal immunogen is a scientific and technologic advance over best vaccination protocols in development for LD that currently rely on parenteral inoculation of a minimum of 3 doses over 1 year. Our preliminary studies show that intranasal administration of a modified OspA vaccine delivered by the laboratory strain WR-PIV5 viral vector (WR-PIV5-OspABPBPk) via prime-boost (2 doses), produces an immune response that is 100% protective against tick transmitted B. burgdorferi infection in mice challenged 4 months after the 1st dose. PIV5 is a safe delivery vector used to develop many vaccines, one of which is undergoing a human clinical trial. The commercialization potential and societal impact of developing a novel, safe and efficacious LD vaccine that can be delivered by a non-invasive method is highly significant given that it may induce more durable immune responses, it could diminish vaccine hesitancy and increase vaccine compliance, and it could enable self-administration of one or both doses. The novelty of the vaccine proposed in this Direct to Phase II SBIR application relates to: 1) the use of a modified full length OspA protein in which the putative autoantigenic epitope has been replaced; 2) a needle-free intranasal delivery method in a safe, highly immunogenic viral vector; 3) the reduced number of immunizations; 4) ease of administration; and 5) the potential to increase immunity longevity. We propose to develop a new viral vector expressing OspABPBPk based on the PIV5 vaccine strain (CPI) and evaluate intranasal vaccine efficacy in mice as compared to the WR-PIV5- ABPBPk shown in preliminary results; we will also assess immunogenicity, safety and efficacy of the best vaccine candidate in the non-human primate (NHP) model of Lyme disease; last, we will perform studies required for Investigational New Drug (IND) regulatory approval by FDA. Once the novel vaccine is shown to meet pre-set performance criteria specified in our milestones (>80% efficacy in mice and non-human primate models), it will be trademarked as LymeMist™ and the company will implement a plan to commercialize it.

抽象的 我们建议开发鼻内，Parainfluenza 5（PIV5）病毒载体传送的疫苗 针对人类莱姆病（LD），以使用Prime-Boost时间表进行管理 市场。 CDC最近对LD的新估计将新数字定为476,000年 案件，高于2015年的329,000，强烈表明美国人的数量受影响 通过这种载体传播疾病正在增加。目前，没有人类莱姆病疫苗 在市场上可用。鼻内免疫原的促进疫苗接种是科学的 以及目前为LD开发的最佳疫苗接种协议的技术进步 依靠父母接种至少1年的3剂。我们的初步研究 证明实验室输送的修饰的OSPA疫苗的鼻内给药 WR-PIV5病毒载体（WR-PIV5-ospaBPBPK）通过Prime-Boost（2剂）产生 免疫反应100％保护免受tick虫的爆发b。brgdorferi感染。 小鼠在第1剂剂量后4个月提出质疑。 PIV5是用于开发的安全交付向量 许多疫苗正在接受人类临床试验。商业化 开发一种新颖，安全有效的LD疫苗的潜在和社会影响可能是 鉴于它可能会诱发更耐用 免疫反应，它可能会减少疫苗犹豫并增加疫苗的依从性，并且 可以实现一种或两种剂量的自我管理。提出的疫苗的新颖性 这直接涉及II阶段SBIR应用程序与以下方面有关的应用程序 推定的自身抗原表位的蛋白质已被取代； 2）无针 安全，高度免疫原性病毒载体中的鼻内递送方法； 3）减少的数量 免疫； 4）易于管理； 5）增加免疫力寿命的潜力。 我们建议开发一种基于PIV5疫苗表达OspabPBPK的新病毒载体 与WR-PIV5-相比，应变（CPI）并评估小鼠鼻内疫苗效率 初步结果中显示的ABPBPK；我们还将评估免疫原性，安全性和效率 莱姆病非人类灵长类动物（NHP）模型中最好的疫苗候选者；最后，我们 FDA将进行研究新药（IND）调节性批准所需的研究。 一旦显示出新的疫苗符合我们在我们的预设绩效标准 里程碑（在小鼠和非人类灵长类动物模型中> 80％的效率），将其标记为 Lymemist™和该公司将实施一项计划以商业化。