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) 它的影响 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) HPV 相关癌症对中低收入国家 (LMIC) 的影响尤为严重。 全球所有新发癌症病例中的 4.5%、90% 的 HPV 相关宫颈癌死亡发生在中低收入国家，并且仅 1% 的中低收入国家拥有保护范围有限的疫苗接种计划 保护范围最广泛的疫苗。 市场上默克公司的 Gardasil-9 只能预防 9 种 HPV 病毒株，不能预防 HPV 病毒株 由于其在中低收入国家中流行，目前的疫苗也成本高昂且难以分发到中低收入国家。 热稳定性和 3 剂量方案当前疫苗的局限性和 HPV 对 LMIC 的负担。 强调需要能够在 LMIC 中有效部署的新型廉价 HPV 疫苗。 这满足了对 HPV 疫苗的需求，该疫苗成本低廉、具有广泛的保护作用，并且对有针对性的两个方面有效： 我们的候选疫苗在我们的专利平台上展示了​​高度保守的 HPV L2 抗原。 使用病毒样颗粒 (VLP) 和重组免疫复合物 (RIC) 的 HPV L2 抗原。 在小鼠和兔子中显示可预防多达 22 种 HPV，并已在人体 I 期中进行了评估 我们的疫苗是使用优化的植物表达系统生产的，可降低制造成本。 （估计每剂不到 0.5 美元，而 Gardasil-9 则为每剂 160 美元），从而在 4-5 天内产生高水平的蛋白质 没有人类或动物病原体污染的天数，我们的临床前小鼠疫苗接种研究。 候选药物已证实其在短短两年内即可产生高抗体滴度和病毒中和的功效 我们的疫苗平台的进一步测试表明，无需注射即可产生保护性免疫。 我们 STTR 第一阶段项目的目标是进行概念验证研究来表征。 VaxSyna 的 HPV 癌症疫苗的配方是一种针对所有临床对象的广谱 HPV 疫苗 温度稳定性是针对 LMIC 的疫苗的一个重要特性。 因此，我们的母奖目标 1 将评估我们的 VLP 和 RIC 疫苗成分的热稳定性。 家长病房目标2将比较小鼠后产生的抗体和中和抗体滴度 与建议的行政补充剂相比，VLP 与 RIC 的不同比例进行疫苗接种。 目标 3 将评估 VaxSyna 的 HPV 疫苗能否成功赋予针对棉尾兔的保护性免疫力 乳头状瘤病毒在HPV标准动物模型新西兰白兔中通过测量抗体、中和 抗体、细胞反应和乳头状瘤几何体积第一阶段项目的成功完成。 对于启动我们提议的涉及​​ IND GMP 前生产和动物毒理学的 II 期研究至关重要 VaxSyna的HPV疫苗成功获批后，我们的低成本和广谱优势。 保护将使 VaxSyna 能够为中低收入国家的个体预防 HPV 引起的癌症。