Development of improved preventative therapeutic strategies for the control of infectious disease

这项澳大利亚奖学金申请的一个主要目标是提供一种机制，使我在职业生涯中第一次能够全身心地投入到我的研究计划中。这一计划解决了一个具有全球意义的问题，即细菌传染病的控制。尽管抗菌药问世已有60多年，但这些疾病继续在全球造成大规模的发病率和死亡率，并对人类健康构成严重威胁。世卫组织估计，细菌感染每年造成1000万人死亡，其经济影响是不可估量的。对于大多数主要病原体，疫苗要么无法获得，要么存在严重缺陷。对常用抗菌素的抗药性正在以惊人的速度增加，现代旅行帮助高抗药性和剧毒克隆在全球迅速传播。由于人类引起的环境变化以及更易受感染的人口比例增加，预计发病率和死亡率也将增加。21世纪细菌传染病的有效管理将需要双管齐下，包括开发更便宜、更有效的疫苗，以及对已知耐药机制难以奏效的新型抗感染药物。然而，制定最佳的治疗和预防策略需要彻底了解疾病的生物学，特别是细菌病原体与其人类宿主之间的复杂相互作用。我还在建立肺炎球菌疫苗联盟中发挥了领导作用，该联盟刚刚向Path疫苗解决方案提交了一套协调的多中心提案，以资助我们开发的基于蛋白质的肺炎球菌疫苗的最终临床前测试、GMP扩大和I-II-III阶段试验。PATH加速肺炎球菌疫苗开发计划具有巨大的潜在意义，因为现在肺炎球菌蛋白疫苗快速进入人体试验的可能性非常大。我们的目标是建立一条从合作者实验室的抗原发现到临床的直接管道。如果成功，这些疫苗可以拯救数百万人的生命。这对我个人来说将是巨大的满足感，因为正是我最初提出并证明了肺炎球菌蛋白的疫苗潜力的“原则证据”，20多年来，我一直在倡导评估其对人类的保护效果。因此，获得澳大利亚奖学金无疑将进一步支持澳大利亚医学研究的国际化。

A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bacterial infections are responsible for >10 million deaths p.a., and the economic impact is inestimable. For most major pathogens, vaccines are either unavailable or have serious shortcomings. Resistance to commonly used antimicrobials is increasing at an alarming rate, and modern travel has assisted the rapid global dissemination of highly resistant and virulent clones. Morbidity and mortality are also predicted to increase as a consequence of human-induced environmental changes and the growing proportion of the population with increased susceptibility to infection. Effective management of bacterial infectious diseases in the 21st century will require a two-pronged approach involving the development of cheaper and more effective vaccines, as well as novel anti-infectives refractory to known resistance mechanisms. However, formulation of optimal therapeutic and preventative strategies demands a thorough understanding of the biology of disease, particularly the complex interactions between bacterial pathogens and their human hosts. I have also played a leadership role in establishing the Pneumococcal Vaccine Consortium, which has just submitted a co-ordinated suite of multicentre proposals to PATH Vaccine Solutions to fund final preclinical testing, GMP scale-up and Phase I-II-III trials of protein-based pneumococcal vaccines that we have developed. The PATH accelerated pneumococcal vaccine development program is of enormous potential significance, because there is now a very real probability of pneumococcal protein vaccines being fast-tracked into human trials. Our aim is to create a direct pipeline from antigen discovery in the collaborators’ laboratories into the clinic. If successful, these vaccines could save millions of lives. This will be of enormous satisfaction to me personally, as it was I who originally proposed and demonstrated “proof of principle” for the vaccine potential of pneumococcal proteins, and I have been advocating assessment of their protective efficacy in humans for over 20 years. Thus, receipt of an Australia Fellowship will undoubtedly further support the internationalisation of Australian medical research.