Mucosal delivery of Clostridium spores encoding recombinant overlapping peptides of HPV antigen as therapeutic vaccines for cervical cancer

“HPV是最常见的性传播感染，超过三分之二的人口在一生中的某个阶段感染了HPV。大多数感染在几个月内就会消失，没有症状；然而，感染高危类型的HPV可能会导致癌症的发展，例如宫颈癌。针对这些高危类型的疫苗现已可用，这些疫苗正在大多数高收入国家和中国使用，以保护有感染风险的女孩和妇女。虽然这样的干预措施是推荐的，并导致了宫颈癌发病率的下降，但这种方法也有缺点。疫苗的稳定性很差，接种疫苗的方式(肌肉注射)在病毒通常进入人体的部位没有提供良好的保护。关键是，这些疫苗的高昂成本极大地限制了它们在HPV感染最普遍的低收入国家的使用。在这个项目中，Chain Biotech Ltd，一家在开发基于梭状芽孢杆菌的疗法方面具有专业知识的微生物公司，正在与牛津大学经验丰富的免疫学研究人员合作，以克服现有疫苗的局限性。其目的是开发一种口服疫苗接种方法，以防止HPV感染，并治疗已经感染该病毒的人。通过摄入无害细菌将疫苗直接输送到胃肠道(GIT)的粘膜表面，克服了胃内低pH和富含酶的环境，这将摧毁其他口服疫苗。如果成功，该方法将比目前的疫苗接种战略有很大改进。它是非侵入性的，将允许大规模接种疫苗，而不会有通过针头损伤传播血液传播感染的风险，并且可以由非医务人员进行管理。如果该方法成功，该项目将有可能扩大这项技术，以开发针对其他对全球健康构成挑战的病毒和细菌感染的疫苗，例如艾滋病毒、埃博拉或霍乱。还有可能开发以摧毁癌细胞为目标的治疗性疫苗。

"HPV is the most commonly sexually transmitted infection with over two-thirds of the population infected at some stage during life. Most infections are cleared without symptoms within a few months; however, infections with high risk types of HPV can lead to development of cancer in for example the cervix. Vaccination against these high-risk types is now available and these vaccines are being used in most high income countries and China to protect girls and women at risk of infection. While such interventions are recommended and have led to a decrease in cervical cancer incidence, the approach also has disadvantages. Stability of the vaccines is poor and the way in which the vaccines are given (by injection into muscle) does not give good protection at the sites where the virus normally enters the body. Critically, the high cost of these vaccines greatly limits their use in low income countries, where HPV infection is most prevalent.In this project, CHAIN Biotechnology Ltd, a microbiome company with expertise in developing _Clostridium_-based therapeutics, is collaborating with experienced immunological researchers from the University of Oxford to overcome limitations of currently available vaccines. The aim is to develop an oral vaccination approach to prevent HPV infection and also to treat people already affected by the virus. Delivery of vaccine directly to the mucosal surfaces of the gastrointestinal tract (GIT) via ingestion of harmless bacteria, overcomes the low pH and enzyme-enriched environment in the stomach that would destroy other oral vaccines. If successful, the approach provides a substantial improvement over the current vaccination strategies. It is non-invasive and would allow mass vaccination without the risk of spreading blood-borne infection by needle injuries, and administration could be performed by non-medical personnel. If the approach is successful, the project will give rise to the possibility of extending this technology to develop vaccines against other viral and bacterial infections that present challenges to global health such as for example HIV, Ebola or cholera. There is also the possibility to develop therapeutic vaccines that target the destruction of cancer cells."