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.

摘要 我们建议开发鼻腔副流感5型(PIV5)病毒载体递送疫苗 抗人类莱姆病(LD)将在美国使用主要增强时间表进行管理 市场。美国疾病控制与预防中心最近对LD的最新估计显示，新的数字为每年476,000人 病例，高于2015年的329,000例，这有力地表明受影响的美国人的数量 由这种媒介传播的疾病正在增加。目前，还没有人类莱姆病疫苗 在市场上有售。用鼻腔免疫原加强接种是一种科学的方法 以及目前正在开发的LD最佳疫苗接种方案的技术进步 依靠非肠道接种，在一年内至少接种3剂。我们的初步研究 显示鼻腔注射实验室提供的改良OspA疫苗 WR-PIV5株病毒载体(WR-PIV5-OspABPBPk)经Prime-Boost(2剂)，产生 对蜱传的伯氏杆菌感染有100%保护作用的免疫应答 小鼠在第一次服药后4个月接受挑战。PIV5是一种安全的传递媒介，用于开发 许多疫苗，其中一种正在进行人体临床试验。商业化 开发一种新的、安全有效的LD疫苗的潜在和社会影响 通过非侵入性方法交付是非常重要的，因为它可能会导致更持久的 免疫反应，它可以减少疫苗的犹豫不决，提高疫苗的依从性，而且它 可以实现一剂或两剂的自我给药。年提出的疫苗的新颖性 这种直接到第二阶段SBIR的应用涉及：1)使用经修改的全长OspA 假定的自身抗原表位已被替换的蛋白质；2)无针 一种安全、高免疫原性病毒载体的鼻腔给药方法；3)减少 免疫接种；4)易于管理；5)增加免疫寿命的可能性。 我们建议在PIV5疫苗的基础上开发一种表达OspABPBPk的新型病毒载体 并与WR-PIV5比较，评价小鼠鼻内疫苗的免疫效果。 ABPBPk在初步结果中显示；我们还将评估免疫原性、安全性和有效性 莱姆病非人类灵长类(NHP)模型的最佳候选疫苗；最后，我们 将进行FDA监管批准的研究新药(IND)。 一旦新型疫苗被证明符合我们的 里程碑(在小鼠和非人类灵长类动物模型中80%的疗效)，它将被注册为 LymeMist™和该公司将实施一项将其商业化的计划。