Global GAS Vaccine Based On The M-Protein

描述（由申请人提供）： 化脓性链球菌（Streptococcus pyogenes），也称为A组链球菌（Group A Streptococcus，GAS），是革兰氏阳性细菌病原体，其引起许多疾病，包括相对良性的咽炎和皮肤感染，严重的侵袭性疾病包括坏死性筋膜炎和感染后后遗症风湿热、风湿性心脏病和肾小球肾炎。目前，还没有在欠发达国家证明有效的初级预防战略，因此显然需要疫苗。正在制定的一些疫苗战略在欠发达国家可能无效。我们的长期目标是开发广谱全球疫苗，预防GAS感染及其相关疾病，包括风湿热。我们的GAS候选疫苗是基于来自M蛋白保守区的肽抗原。 我们有四种使用这种抗原的潜在疫苗构建体，每一种都在临床前研究中显示出良好的免疫原性、安全性和保护性。 当前应用程序中的工作有三个总体目标： (1)我们最先进的结构进展到临床试验。 在这项工作结束时，我们预计将完成： (a)在澳大利亚成人志愿者中进行的初步I期试验。 (b)一项在澳大利亚成年志愿者和 发展中国家。 (c)在发展中国家的儿童志愿者中进行的小型I期试验。 (2)保守区肽作为鼻内疫苗的进一步开发。 (3)在发展中国家进行实地研究，以确定可分阶段使用的保护相关因素 II和III的保守区肽的临床试验，并建立一个领域的网站，这些后期阶段的试验。

DESCRIPTION (provided by applicant): Streptococcus pyogenes which is also known as Group A Streptococcus (GAS) is a Gram positive bacterial pathogen that is responsible for numerous diseases including relatively benign pharyngitis and skin infections to serious invasive diseases including necrotizing fasciitis and the post-infectious sequelae rheumatic fever, rheumatic heart disease and glomerulonephritis. Presently, there is no strategy for primary prevention that is proven to work in less-developed countries, so a vaccine is clearly needed. Some vaccine strategies under development may not be effective in less developed countries. Our long-term goal is the development of broad-spectrum global vaccine that prevents GAS infection and its associated diseases, including rheumatic fever. Our GAS vaccine candidate is based on a peptide antigen from the conserved region of the M-protein. We have four potential vaccine constructs that use this antigen, each of which has shown good immunogenicity, safety and protection in pre-clinical studies. There are three overall objectives for the work in the current application: (1) Progression of the most advanced of our constructs to clinical trials. At the conclusion of this work, we expect to have completed: (a) An initial phase I trial in adult volunteers in Australia. (b) A larger multicentre phase I trial in adult volunteers in Australia and adult volunteers in a developing country. (c) A small phase I trial in child volunteers in a developing country. (2) Further development of the conserved region peptide as an intranasal vaccine. (3) Field studies in a developing country to establish correlates of protection that may be used in phase II and III clinical trials of the conserved region peptide, and to establish a field site for these later-phase trials.