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1.8万例感染病例和2000例死亡病例。在世界其他地区，发病率要高得多，主要是因为出现了高度产毒、对抗生素具有抗药性的菌株。艰难梭菌感染每年在美国造成约300万例腹泻和结肠炎。在英国，超过80%的艰难梭菌感染发生在65岁以上的人群中。因此，口服疫苗为老龄化人口提供了一种方便的预防措施，目前还没有艰难梭菌的疫苗。反复感染ETEC会导致发展中国家儿童营养不良、生长发育迟缓和认知障碍。在成人中，包括旅行者，腹泻可导致胃肠紊乱、反应性关节炎，甚至严重的、使人虚弱的炎症性肠病。目前还没有批准用于ETEC的疫苗，尽管霍乱疫苗杜科拉具有一些交叉反应，而且ETEC毒株覆盖范围非常有限。Prokaurum的Typhetec疫苗承诺100%覆盖ETEC的已知毒株。目前有两种伤寒疫苗：注射Vi疫苗和口服减毒活疫苗Vivotif。基于可能具有更少的副作用、更低的成本和口服递送，我们估计Typhetec最初可以占据伤寒旅行者市场至少20%的份额。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一个精确、合理设计的活细菌递送和表达平台。瓦克森氏菌专门针对肠道的免疫细胞，一旦被吞噬，就以受控的方式表达它们的重组蛋白疫苗。它承诺使许多重组蛋白疫苗可以口头交付，同时消除下游蛋白纯化，从而减少大部分开发成本。

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.