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

基本信息

批准号：
10477108
负责人：
Mary Pardhe
金额：
$ 31.59万
依托单位：
VAXSYNA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10477108
关键词：
Accounting Address Adjuvant Affect Animal Model Animals Antibodies Antibody Response Antibody titer measurement Antigen-Antibody Complex Antigens Anus Arizona CD8-Positive T-Lymphocytes Cancer Etiology Cancer Vaccines Cervical Cessation of life Characteristics Chemicals Circular Dichroism Collaborations Complex Country Data Development Diagnosis Dose Economic Burden Electrophoresis Epitopes Female Flow Cytometry Formulation Funding Gardasil Goals Head and neck structure Hepatitis B Core Antigen Hour Human Human Papilloma Virus Vaccine Human Papilloma Virus-Related Malignant Neoplasm Human Papillomavirus Human papillomavirus 6 Immune Immune response 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 Monoclonal Antibodies Mus Oropharyngeal Oryctolagus cuniculus Papillomavirus Phase Plants Polyacrylamide Gel Electrophoresis Positioning Attribute Prevalence Proteins Public Health Recombinants Regimen Safety Schedule Serum Small Business Technology Transfer Research Sodium Dodecyl Sulfate System Technology Temperature Testing Tonsil United States United States National Institutes of Health Universities Vaccination Vaccine Production Vaccines Vagina Viral Virus-like particle Woman cancer type clinically relevant comparative efficacy cost cost estimate design efficacy testing high risk immunogenic immunogenicity innovation male malignant oropharynx neoplasm mouse model neutralizing antibody novel pathogen phase 2 study phase I trial pre-clinical prevent protein structure response screening tongue root ultraviolet vaccine candidate vaccine formulation vaccine platform vaccine strategy vaccine trial

项目摘要

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, and 90% of HPV-related cervical cancer deaths occur in LMIC. The global economic burden of HPV is especially serious in LMIC where cervical screening and vaccination is not easily obtainable. Only 1% of LMIC have vaccination programs and current vaccines are limited in their 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, such as HPV-35. 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 an HPV vaccine candidate 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 this 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 Aim 1 will assess the thermal stability of both our VLP and RIC vaccine components. If one platform is more stable than the other, we will adjust our vaccine formulation accordingly in Aim 2. 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. The successful completion of this Phase I project is critical to initiate our proposed Phase II studies involving pre-IND GMP manufacturing strategies and testing within the same animal models used to validate current vaccines. 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、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 4.5% 的新癌症病例和 90% 的 HPV 相关宫颈癌死亡发生在中低收入国家。 HPV 的全球经济负担在中低收入国家尤其严重，因为这些国家没有进行宫颈筛查和疫苗接种只有 1% 的中低收入国家有疫苗接种计划，而且现有疫苗的广度有限。默克公司的 Gardasil-9 是市场上保护范围最广的疫苗，只能预防 9 种疾病。 HPV 病毒株并不能预防中低收入国家中流行的病毒株，例如 HPV-35。由于其热稳定性和 3 剂量方案，向 LMIC 分发成本高昂且具有挑战性。当前疫苗的局限性和 HPV 对中低收入国家的负担强调了对新的更便宜的 HPV 疫苗的需求 VaxSyna, Inc 的 HPV 候选疫苗可以有效地部署在 LMIC 中。我们的候选疫苗成本低、保护范围广且有效，并有针对性的两剂注射计划。在我们的专利平台上展示高度保守的 HPV L2 抗原，该平台使用病毒样颗粒 (VLP) 和重组免疫复合物 (RIC) 已被证明可以预防多达 22 种类型的 HPV。我们的疫苗是使用小鼠和兔子体内的 HPV 进行生产的，并已在人体 I 期试验中进行了评估。优化的植物表达系统可降低制造成本（预计每剂成本低于 0.5 美元） Gardasil-9 的价格为 160 美元/剂），无需人类或动物即可在 4-5 天内产生高水平的蛋白质我们的候选药物的临床前小鼠疫苗接种研究已证实其功效。只需两剂疫苗即可产生高抗体滴度和病毒中和效果。平台表明，无需化学佐剂即可实现保护性免疫的目标。 STTR 第一阶段项目旨在进行概念验证研究，以表征 VaxSyna 的配方 HPV 癌症疫苗是一种广谱 HPV 疫苗，针对所有临床相关的 HPV。稳定性是针对中低收入国家的疫苗的一个重要特征，因此，我们的目标 1 将评估其稳定性。我们的 VLP 和 RIC 疫苗成分的热稳定性如果一个平台比另一个平台更稳定，我们就会这样做。将在目标 2 中相应调整我们的疫苗配方。目标 2 将比较抗体和中和抗体与 Gardasil-9 相比，小鼠接种不同比例的 VLP 与 RIC 后产生的滴度。成功完成第一阶段项目对于启动我们拟议的涉及预 IND 的第二阶段研究至关重要 GMP 生产策略和在用于验证当前疫苗的相同动物模型中进行测试。 VaxSyna HPV疫苗成功获批后，我们的低成本、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。