Global GAS Vaccine Based On The M-Protein

描述(由申请人提供)： 化脓性链球菌又称A组链球菌(GAS)，是一种革兰氏阳性细菌，可引起多种疾病，包括相对良性的咽炎和皮肤感染，以及严重的侵袭性疾病，包括坏死性筋膜炎和感染后的后遗症风湿热、风湿性心脏病和肾炎。目前，没有被证明在欠发达国家有效的初级预防战略，因此显然需要疫苗。一些正在开发中的疫苗策略在欠发达国家可能并不有效。我们的长期目标是开发广谱的全球疫苗，以预防气体感染及其相关疾病，包括风湿热。我们的GAS候选疫苗是基于M蛋白保守区的多肽抗原。我们有四种使用这种抗原的潜在疫苗结构，在临床前研究中，每一种都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入临床试验的进展。在这项工作结束时，我们预计已完成： (A)在澳大利亚的成年志愿者中进行第一阶段的初步试验。 (B)在澳大利亚的成人志愿者和澳大利亚的成人志愿者中进行更大规模的多中心第一阶段试验 发展中国家。 (C)在发展中国家的儿童志愿者中进行第一阶段的小规模试验。 (2)保守区多肽作为鼻腔疫苗的进一步发展。 (3)在发展中国家进行实地研究，以建立可用于保守区多肽的第二阶段和第三阶段临床试验的保护相关性，并为这些后期试验建立一个现场地点。

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.