Low cost, Broad Spectrum Cancer Vaccine Targeting Human Papillomavirus

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，以及3） 对中低收入国家（LMIC）的影响。HPV相关的癌症是导致 全球所有新发癌症病例的4.5%，90%的HPV相关宫颈癌死亡发生在LMIC， 1%的低收入中等收入国家有保护范围有限的疫苗接种计划。最广泛的保护性疫苗 在市场上，默克公司的Gardasil-9只能预防九种HPV病毒株，不能预防病毒株。 在低收入国家很普遍。目前的疫苗也是昂贵的和具有挑战性的分配给LMIC，由于其 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 强调了需要新的更便宜的HPV疫苗，可以有效地部署在LMIC。VaxSyna，Inc HPV疫苗解决了这一需求，它是低成本的，广泛的保护，有效的靶向两个- 给药时间表。我们的候选疫苗在我们的专利平台上显示高度保守的HPV L2抗原 它使用病毒样颗粒（VLP）和重组免疫复合物（RIC）。HPV L2抗原已被 在小鼠和兔子中显示出对多达22种类型的HPV的保护作用，并已在人类I期中进行了评估 审判我们的疫苗使用优化的植物表达系统生产，降低了生产成本 （估计低于0.5美元/剂，而Gardasil-9为160美元/剂），从而在4 - 5天内产生高水平的蛋白质。 无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 候选人已经证实了其在产生高抗体滴度和病毒中和方面的功效， 剂量对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。我们的STTR第一阶段项目的目标是进行概念验证研究， VaxSyna的HPV癌症疫苗的配方是一种广谱HPV疫苗， 相关HPV。温度稳定性是针对LMIC的疫苗的重要特征。作为 因此，我们的母公司Aim 1将评估VLP和RIC疫苗组分的热稳定性。为 父母病房Aim 2将比较小鼠接种后产生的抗体和中和抗体滴度 与Gardasil-9相比，VLP与RIC的不同比例的疫苗接种。拟议的行政补充 目的3将评估VaxSyna的HPV疫苗是否成功地赋予对棉尾兔的保护性免疫 HPV-标准动物模型新西兰白色兔通过测量抗体、中和 抗体、细胞反应和乳头状瘤几何体积。第一期工程的顺利完成 对于启动我们提出的涉及IND前GMP生产和动物毒理学的II期研究至关重要 问题研究在VaxSyna的HPV疫苗成功获得批准后，我们的低成本和广谱优势 保护将使VaxSyna能够预防LMIC中个体的HPV引起的癌症。

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.