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4.5%的新发癌症病例和90%的HPV相关宫颈癌死亡发生在LMIC。的 HPV的全球经济负担在LMIC中尤其严重，因为在LMIC中， 容易获得。只有1%的LMIC有疫苗接种计划，目前的疫苗在广度上有限 保护。市场上最广泛的保护性疫苗，默克公司的Gardasil-9，只能保护9种 HPV毒株，并且不能预防LMIC中流行的毒株，如HPV-35。当前疫苗 由于它们的热稳定性和3剂量方案，分配给LMIC也是昂贵和具有挑战性的。的 目前疫苗的局限性和HPV对LMIC的负担强调了对新的更便宜的HPV疫苗的需求 可以有效地部署在LMIC中。VaxSyna公司通过一种HPV候选疫苗解决了这一需求， 是低成本的，广泛的保护，并有效的有针对性的两个剂量的时间表。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，该平台使用病毒样颗粒（VLP）， 重组免疫复合物（RIC）。HPV L2抗原已被证明可以保护多达22种类型 在小鼠和兔子中的HPV感染，并已在人体I期试验中进行了评估。我们的疫苗是用 优化的植物表达系统，降低了生产成本（估计低于0.5美元/剂， Gardasil-9为160美元/剂），从而在4-5天内产生高水平的蛋白质，而无需人类或动物 病原体污染临床前，小鼠疫苗接种研究与我们的候选人已经证实了其疗效 在产生高抗体滴度和病毒中和在短短两个剂量。我们疫苗的进一步测试 平台已经表明，保护性免疫是可能的，而不需要化学佐剂。的目标 该STTR第一阶段项目是进行概念验证研究，以表征VaxSyna的配方 HPV癌症疫苗是一种广谱HPV疫苗，靶向所有临床相关HPV。温度 稳定性是针对LMIC的疫苗的重要特征。因此，我们的目标1将评估 我们的VLP和RIC疫苗组分的热稳定性。如果一个平台比另一个更稳定， 将在目标2中相应调整我们的疫苗配方。目的2将比较抗体和中和抗体 与Gardasil-9相比，用不同的VLP与RIC比率接种小鼠后产生的滴度。的 成功完成这一I期项目对于启动我们提议的II期研究至关重要， 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的测试。 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, 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.