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。人类乳头瘤病毒（HPV）是一个主要的公共卫生问题，因为它的含义是 肛门，子宫颈，口咽，阴茎，外阴和阴道的癌症； 2）全球经济燃烧，3） 对低到中等收入国家（LMIC）的影响不成比例。与HPV相关的癌症负责 在全球所有新癌症病例中，有4.5％，HPV相关的宫颈癌死亡中有90％发生在LMIC中，仅发生 1％的LMIC进行了疫苗接种计划，保护范围有限。最广泛保护的疫苗 在市场上，默克的Gardasil-9仅保护9种HPV菌株，并且不能防止菌株 在LMIC中很普遍。当前的疫苗也很昂贵，并且由于其分配给LMIC而挑战 热稳定性和三剂治疗方案。当前疫苗的局限性和HPV在LMIC上的燃烧 强调了可以在LMIC中有效部署的新型HPV疫苗的需求。 Vaxsyna，Inc 通过低成本，广泛保护和有效的HPV疫苗来满足这种需求 剂量时间表。我们的疫苗候选者在我们的专利平台上显示高度组成的HPV L2抗原 使用颗粒（VLP）和重组免疫复合物（RIC）等病毒。 HPV L2抗原已经 显示可预防小鼠和兔子中多达22种类型的HPV，并已在人类I期进行评估 试验。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 （估计为$ 0.5/剂量，$ 160/剂量/剂量的Gardasil-9），从而在4-5中产生高水平的蛋白质 没有人类或动物病原体污染的天数。临床前小鼠疫苗接种研究 候选人已确认其在产生高抗体滴度和病毒神经化的有效性 剂量。对我们的疫苗平台的进一步测试表明，无需保护的免疫力是可能的 化学调整。我们STTR I期项目的目标是进行概念验证研究以表征 Vaxsyna的HPV癌症疫苗的配方作为广谱HPV疫苗，其针对所有临床 相关的HPV。温度稳定性是针对LMIC的疫苗的重要特征。作为 这样的是，我们的父级AIM 1将评估我们的VLP和RIC疫苗成分的热稳定性。为了 母病房AIM 2将比较小鼠后产生的抗体和中和抗体滴度 与Gardasil-9相比，VLP与RIC的疫苗接种的比率不同。拟议的行政补充 AIM 3将评估Vaxsyna的HPV疫苗对棉尾兔的防护性免疫的成功 HPV标准动物模型新西兰白兔子中的乳头瘤病毒通过测量抗体，中和 抗体，细胞反应和乳头状瘤几何体积。该阶段项目的成功完成 对于启动我们提出的涉及GMP制造和动物毒理学的II期研究至关重要 研究。在成功批准Vaxsyna的HPV疫苗后，我们的低成本优势和广谱 保护将定位Vaxsyna，以防止在LMIC的个体中为HPV引起的癌症。