13TSB_SynBio: Engineering immune-cell-targeting bacteria to express vaccines from within the body

伤寒每年造成2200万例病例和20万人死亡，而ETEC每年造成30万至50万人死亡。2011年，HPA报告了英国18，000例感染病例和2，000例死亡。在世界其他地区，发病率要高得多，主要是由于出现了高致病性的抗生素耐药菌株。C.在美国，艰难梭菌感染每年导致约300万例腹泻和结肠炎。80%以上的C.在英国，艰难梭菌感染是在65岁以上的人群中。因此，口服疫苗接种为老龄人口提供了一种方便的预防措施，目前还没有针对C。ETEC反复感染导致发展中国家儿童营养不良、生长发育迟缓和认知缺陷。在成年人中，包括旅行者，腹泻可导致胃肠道疾病，反应性关节炎，甚至严重和衰弱的炎症性肠病。目前还没有批准用于ETEC的疫苗，尽管Dukoral霍乱疫苗具有一些交叉反应性，并且ETEC菌株覆盖率非常有限。Prokarium的Typhetec疫苗承诺覆盖100%的已知ETEC菌株。目前有两种类型的伤寒疫苗;注射Vi疫苗和口服活减毒疫苗Vivotif。基于副作用少、成本低和口服给药的可能性，我们估计Typhetec最初可以占据至少20%的伤寒旅行者市场。Vaxonella是一个合成生物学平台，利用一套先进的基因技术将沙门氏菌从病原体重新设计为精确、合理设计的活菌递送和表达平台。瓦氏杆菌属细菌特异性地靶向肠道的免疫细胞，并且一旦被吞噬，就以受控的方式表达其重组蛋白疫苗。它有望使许多重组蛋白疫苗口服，同时消除下游蛋白纯化和大部分开发成本。

Typhoid is responsible for 22 million cases and 200,000 deaths annually, while ETEC is responsible for 300,000 - 500,000 deaths pa. In 2011, the HPA reported 18,000 cases of infection and 2,000 deaths in the UK. In other parts of the world, the incidence is much higher, mainly due to the emergence of highly toxigenic, antibiotic resistant strains. C. difficile infection causes ~3 million cases of diarrhoea and colitis annually in the USA. Over 80% of C. difficile infections in the UK are in people over 65. Thus, oral vaccination offers a convenient, preventative measure for the ageing population, and is currently no vaccine for C. difficile.Repeated ETEC infection causes malnutrition, growth stunting and cognitive deficits in children in developing countries. In adults, including travellers, diarrhoea can result in gastrointestinal disorders, reactive arthritis and even severe and debilitating inflammatory bowel disease. There are currently no vaccines approved for ETEC, although the cholera vaccine Dukoral has some cross-reactivity and very limited ETEC strain coverage. Prokarium's Typhetec vaccine promises to cover 100% of the known strains of ETEC. There are currently two types of typhoid vaccines; the injectable Vi vaccine and the oral live attenuated vaccine Vivotif. Based on likely having fewer side effects, lower costs and being orally deliverable, we estimate that Typhetec could initially capture at least 20% of the typhoid travellers market.Vaxonella is a synthetic biology platform that utilises a suite of advanced genetic technologies to re-engineer Salmonella from a pathogen to a precise, rationally designed live bacterial delivery and expression platform. Vaxonella bacteria specifically target the immune cells of the gut, and once engulfed, express their recombinant protein vaccine in a controlled manner. It promises to make many recombinant protein vaccines orally deliverable, while eliminating downstream protein purification and with that the majority of development costs.