Low cost, Broad Spectrum Cancer Vaccine Targeting Human Papillomavirus

针对人乳头瘤病毒的低成本、广谱癌症疫苗

• 批准号: 10650067
• 负责人: Mary Pardhe
• 金额: $ 12.13万
• 依托单位: VAXSYNA, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650067
• 关键词: Accounting; Address; Adjuvant; Administrative Supplement; Affect; Animal Model; Animals; Antibodies; Antibody Response; Antibody titer measurement; Antigen-Antibody Complex; Antigens; Anus; Arizona; Award; CD8-Positive T-Lymphocytes; Cancer Etiology; Cancer Vaccines; Cervical; Cessation of life; Characteristics; Chemicals; Circular Dichroism; Collaborations; Country; Cutaneous; Data; Dose; Economic Burden; Electrophoresis; Female; Formulation; Funding; Gardasil; Gender; Goals; Harvest; Head and neck structure; Hour; Human; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 6; Immune; Immunity; Immunization; Immunization Programs; Immunize; In Vitro; Inbred BALB C Mice; Incidence; Income; Individual; Intramuscular; Investigational Drugs; L2 viral capsid protein; Legal patent; Malignant Neoplasms; Malignant Vaginal Neoplasm; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Malignant neoplasm of penis; Malignant neoplasm of vulva; Measures; Medical; Modeling; Mus; New Zealand; Oropharyngeal; Oryctolagus cuniculus; Papilloma; Papillomavirus; Parents; Persons; Phase; Phase I Clinical Trials; Plants; Polyacrylamide Gel Electrophoresis; Positioning Attribute; Prevalence; Production; Proteins; Public Health; Recombinants; Regimen; Schedule; Serum; Sexually Transmitted Diseases; Small Business Technology Transfer Research; Sodium Dodecyl Sulfate; System; T cell response; Technology; Temperature; Testing; Time; Toxicology; United States National Institutes of Health; Universities; Vaccinated; Vaccination; Vaccine Production; Vaccines; Vagina; Viral; Virus-like particle; cancer type; clinically relevant; comparative efficacy; cost; cost estimate; draining lymph node; efficacy testing; high risk; immunogenic; innovation; low and middle-income countries; male; malignant oropharynx neoplasm; mouse model; neutralizing antibody; nonhuman primate; novel; pathogen; penis; phase 2 study; phase I trial; pre-clinical; prevent; protein structure; response; success; tumor; vaccine candidate; vaccine efficacy; vaccine platform; vaccine trial; ward

Project Summary. Human papillomavirus (HPV) is a major public health concern due to 1) its implication in cancers of the anus, cervix, oropharynx, penis, vulva, and vagina; 2) global economic burden, and 3) vastly disproportionate impact on low-to-middle-income countries (LMIC). HPV-related cancers are responsible for 4.5% of all new cancer cases worldwide, 90% of HPV-related cervical cancer deaths occur in LMIC, and only 1% of LMIC have vaccination programs with limited breadth of protection. The most broadly protective vaccine on the market, Merck’s Gardasil-9, only protects against nine HPV strains and does not protect against strains that are prevalent in LMIC. Current vaccines are also costly and challenging to distribute to LMIC due to their thermal stability and 3-dose regimen. The limitations of current vaccines and burden of HPV on LMIC underscores the need for new cheaper HPV vaccines that can be effectively deployed in LMIC. VaxSyna, Inc addresses this need with a HPV vaccine that is low-cost, broadly protective, and efficacious with a targeted two- dose schedule. Our vaccine candidate displays the highly conserved HPV L2 antigen on our patented platform that uses virus like particles (VLP) and recombinant immune complexes (RIC). The HPV L2 antigen has been shown to protect against up to 22 types of HPV in mice and rabbits and has been evaluated in human phase I trials. Our vaccine is produced using an optimized plant expression system that lowers the manufacturing cost (estimated at less than $0.5/dose vs. $160/dose for Gardasil-9), thereby producing high levels of proteins in 4-5 days without human or animal pathogen contamination. Preclinical, mouse vaccination studies with our candidate have confirmed its efficacy in generating high antibody titers and viral neutralization in as little as two doses. Further tests of our vaccine platform have shown that protective immunity is possible without the need of a chemical adjuvant. The goal of our STTR phase I project is to conduct proof-of-concept studies to characterize the formulation of VaxSyna’s HPV cancer vaccine as a broad-spectrum HPV vaccine that targets all clinically relevant HPVs. Temperature stability is an important characteristic for vaccines that are targeted for LMIC. As such, our parent award Aim 1 will assess the thermal stability of both our VLP and RIC vaccine components. For the parent ward Aim 2 will compare the antibody and neutralizing antibody titers produced after mouse vaccination with varying ratios of VLP to RIC as compared to Gardasil-9. Proposed administrative supplement Aim 3 will evaluate the success of VaxSyna’s HPV vaccine to confer protective immunity against cottontail rabbit papillomavirus in the HPV-standard animal model New Zealand white rabbits by measuring antibody, neutralizing antibody, cellular responses, and papilloma geometric volume. The successful completion of this Phase I project is critical to initiate our proposed Phase II studies involving pre-IND GMP manufacturing and animal toxicology studies. Upon successful approval of VaxSyna’s HPV vaccine, our advantages of low costs and broad-spectrum protection will position VaxSyna to prevent HPV-caused cancers for individuals in LMIC.

项目摘要。人乳头瘤病毒(HPV)是一个主要的公共卫生问题，因为1)它在 肛门癌、子宫颈癌、口咽癌、阴茎癌、外阴癌和阴道癌；2)全球经济负担；3)巨大的 对中低收入国家(LMIC)的影响不成比例。与HPV相关的癌症是 全世界4.5%的新癌症病例，90%与HPV相关的宫颈癌死亡发生在LMIC，并且只有 1%的LMIC有疫苗接种计划，但保护范围有限。保护性最广的疫苗 在市场上，默克公司的Gardasil-9只对九种HPV病毒株有保护作用，而对病毒株没有保护作用 在LMIC中很普遍。目前的疫苗分发给LMIC也是昂贵和具有挑战性的，因为它们 热稳定性和3剂方案。现有疫苗的局限性和HPV对LMIC的负担 强调需要能够有效地在LMIC部署的新的更便宜的HPV疫苗。VaxSyna，Inc. 解决这一需要的是一种低成本、广泛保护和有效的HPV疫苗，它具有靶向的两种- 剂量表。我们的候选疫苗在我们的专利平台上展示高度保守的HPV L2抗原 使用病毒样颗粒(VLP)和重组免疫复合体(RIC)。人乳头瘤病毒L2抗原已经 在小鼠和兔子身上显示了对多达22种HPV的保护作用，并已在人类I期进行了评估 审判。我们的疫苗是使用优化的植物表达系统生产的，该系统降低了制造成本 (估计不到0.5美元/剂，而Gardasil-9为160美元/剂)，从而在4-5个月中产生高水平的蛋白质 没有人类或动物病原体污染的日子。我们的临床前、小鼠疫苗研究 候选人已经证实了它在产生高抗体效价和在短短两年内中和病毒的有效性 剂量。我们疫苗平台的进一步测试表明，保护性免疫是可能的，而不需要 一种化学佐剂。我们STTR第一阶段项目的目标是进行概念验证研究，以 VaxSyna公司的HPV癌症疫苗的配方是一种针对所有临床患者的广谱HPV疫苗 相关的HPV。温度稳定性是针对LMIC的疫苗的重要特征。AS 这样，我们的母公司奖Aim 1将评估我们的VLP和RIC疫苗组件的热稳定性。为 家长Ward Aim 2将比较小鼠产生的抗体和中和抗体效价 与Gardasil-9相比，VLP和RIC比例不同的疫苗接种。拟议的行政补充 目的3将评估VaxSyna的HPV疫苗对棉尾兔产生保护性免疫的成功 HPV标准动物模型新西兰大白兔乳头瘤病毒抗体测定、中和 抗体、细胞反应和乳头状瘤几何体积。本项目一期工程顺利竣工 对启动我们提议的涉及前IND GMP制造和动物毒理学的第二阶段研究至关重要 学习。在成功批准VaxSyna的HPV疫苗后，我们的低成本和广谱的优势 保护将使VaxSyna定位为LMIC中的个人预防HPV引起的癌症。