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)它在 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)巨大的 对中低收入国家(LMIC)的影响不成比例。与HPV相关的癌症是 全世界4.5%的新癌症病例和90%的与HPV相关的宫颈癌死亡发生在LMIC。这个 全球HPV的经济负担在LMIC尤其严重，那里没有进行宫颈筛查和疫苗接种 容易获得的。只有1%的LMIC有疫苗接种计划，目前的疫苗范围有限 是一种保护。市场上保护范围最广的疫苗，默克公司的Gardasil-9，只能预防九种 HPV毒株，不能预防LMIC中流行的毒株，如HPV-35。当前的疫苗 由于其热稳定性和3剂给药方案，分发给LMIC也是昂贵和具有挑战性的。这个 现有疫苗的局限性和HPV对LMIC的负担凸显了新的廉价HPV疫苗的必要性 可以有效地部署在LMIC中。VaxSyna，Inc.通过一种HPV候选疫苗满足了这一需求 低成本，广泛的保护，和有针对性的两剂时间表有效。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，使用病毒样颗粒(VLP)和 重组免疫复合物(RIC)。人类乳头状瘤病毒L2抗原已被证明可抵抗多达22种类型的病毒 在小鼠和兔子身上发现了人乳头瘤病毒，并在人类I期试验中进行了评估。我们的疫苗是用一种 优化的植物表达系统，降低了制造成本(估计每剂不到0.5美元，而 Gardasil-9的每剂160美元)，从而在没有人或动物的情况下在4-5天内产生高水平的蛋白质 病原体污染。与我们的候选人进行的临床前小鼠疫苗接种研究证实了它的有效性 在产生高抗体效价和病毒中和方面，只需两次剂量。对我们的疫苗进行进一步测试 Platform的研究表明，保护性免疫是可能的，而不需要化学佐剂。的目标是 该STTR第一阶段项目将进行概念验证研究，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。温度 稳定性是针对LMIC的疫苗的一个重要特征。因此，我们的目标1将评估 我们的VLP和RIC疫苗组件的热稳定性。如果一个平台比另一个平台更稳定，我们 我将在目标2中相应地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，用不同比例的VLP和RIC接种小鼠后产生的效价。这个 成功完成这一第一阶段项目对于启动我们拟议的第二阶段研究至关重要，该阶段研究涉及IND前 GMP生产策略和在用于验证当前疫苗的相同动物模型中的测试。 在成功批准VaxSyna的HPV疫苗后，我们的低成本和广谱的优势 保护将使VaxSyna定位为LMIC中的个人预防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.