Intranasal Vaccine Against Lyme Disease

莱姆病鼻内疫苗

• 批准号: 10664036
• 负责人: Maria Gomes-Solecki
• 金额: $ 100万
• 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/10664036
• 关键词: Adult; Affect; American; Animal Model; Antigens; Biological Assay; Borrelia burgdorferi; COVID-19; COVID-19 vaccine; 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; Marketing; Methods; Modeling; Monkeys; Mus; Needles; New Drug Approvals; OspA protein; OspA vaccine; Parainfluenza; Performance; Phase; Phase I Clinical Trials; Primates; Production; Qualifying; Research; Safety; Schedule; Self Administration; Small Business Innovation Research Grant; Specific qualifier value; Technology; Ticks; Tissues; Trademark; Vaccination; Vaccines; Vector-transmitted infectious disease; Vero Cells; Viral Vector; aluminum sulfate; cell bank; commercialization; delivery vehicle; immunogenic; immunogenicity; nonhuman primate; novel; novel vaccines; pre-clinical assessment; preclinical study; prevent; response; subcutaneous; tick transmission; timeline; 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 我们建议开发鼻内副流感 5 (PIV5) 病毒载体疫苗 在美国，针对人类莱姆病 (LD) 采用初免-加强方案进行管理 CDC 最近对 LD 的最新估计表明，新的数字为每年 476,000 例。 病例数高于 2015 年的 329,000 例，这强烈表明受影响的美国人数量 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。 市场上有售的鼻内免疫原强化疫苗是一种科学的疫苗。 以及目前正在开发的 LD 最佳疫苗接种方案的技术进步 我们的初步研究依赖于 1 年内至少 3 剂的肠外接种。 表明鼻内施用实验室提供的改良 OspA 疫苗 菌株 WR-PIV5 病毒载体 (WR-PIV5-OspABPBPk) 通过初免-加强（2 剂），产生 免疫反应可 100% 防止蜱传播的伯氏疏螺旋体感染 小鼠在第一次注射 4 个月后受到攻击，PIV5 是用于开发的安全递送载体。 多种疫苗，其中一种正在进行人体临床试验。 开发一种新型、安全且有效的 LD 疫苗的潜在和社会影响 通过非侵入性方法提供非常重要，因为它可能会导致更持久的 免疫反应，它可以减少疫苗犹豫并提高疫苗依从性，并且 可以实现自行注射一剂或两剂疫苗。 该 Direct to Phase II SBIR 申请涉及：1) 使用修改后的全长 OspA 推定的自身抗原表位已被替换的蛋白质 2) 无针； 安全、高免疫原性病毒载体的鼻内递送方法；3) 减少数量； 免疫接种；4) 易于给药；5) 延长免疫力的潜力。 我们建议基于PIV5疫苗开发表达OspABPBPk的新病毒载体 菌株（CPI）并评估与 WR-PIV5- 相比的小鼠鼻内疫苗功效 初步结果显示的 ABPBPk；我们还将评估其免疫原性、安全性和有效性。 最后，我们是莱姆病非人类灵长类动物 (NHP) 模型中的最佳候选疫苗； 将进行 FDA 试验性新药 (IND) 监管批准所需的研究。 一旦新型疫苗被证明符合我们的预先设定的性能标准， 里程碑（在小鼠和非人类灵长类动物模型中功效>80%），它将被商标为 LymeMist™ 和公司将实施一项将其商业化的计划。