Global GAS Vaccine Based On The M-Protein

基于 M 蛋白的全球 GAS 疫苗

• 批准号: 7493529
• 负责人: Michael F Good
• 金额: $ 51.29万
• 依托单位: QUEENSLAND INSTITUTE OF MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7493529
• 关键词: Acute; Acute Disease; Acute Rheumatic Heart Disease; Adjuvant; Adult; Age; Antibodies; Antibody Formation; Antigens; Australia; Autoimmune Process; Benign; Categories; Child; Class; Clinical; Clinical Trials; Compatible; Control Groups; Country; Cyclic GMP; Data; Developed Countries; Developing Countries; Development; Development, Other; Diphtheria; Disease; Drug Formulations; Effectiveness; Epidemiology; Epitopes; Evaluation; Fiji; Funding; Glomerulonephritis; Goals; Guanosine Monophosphate; HLA-DR2 Antigen; HLA-DR3 Antigen; Human; Immune; Immune response; Immunoglobulin A; Immunoglobulin G; In Vitro; Incidence; Industry; Infectious Skin Diseases; Intellectual scale; Invasive; Licensing; Lipids; Longevity; Marketing; Measures; Mediating; Medical Surveillance; Mind; Modeling; Morbidity - disease rate; Mus; N-terminal; Necrotizing fasciitis; Numbers; Orphan; Pathogenesis; Patients; Peptides; Pharmacologic Substance; Pharyngeal structure; Pharyngitis; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Population; Positioning Attribute; Post-Streptococcal Glomerulonephritis; Prevention; Primary Prevention; Process; Production; Property; Public Health; Pyoderma; Rate; Reaction; Research; Research Infrastructure; Research Personnel; Rheumatic Fever; Rheumatic Heart Disease; Role; Route; Safety; School-Age Population; Series; Serological; Serum; Site; Skin; Streptococcal Infections; Streptococcal Vaccines; Streptococcus pyogenes; Surface; Surveys; T-Lymphocyte; Testing; Toll-like receptors; Toxicology; Toxoids; Transgenic Mice; Vaccination; Vaccine Clinical Trial; Vaccines; Variant; Work; aluminum sulfate; analytical method; base; cohort; cross reactivity; falls; field study; human tissue; immunogenicity; in vivo; interest; lymph nodes; method development; mortality; multicatalytic endopeptidase complex; multiple myeloma M Protein; mutant; pathogen; pre-clinical; preclinical study; prevent; programs; prospective; respiratory; scale up; size; vaccine development; volunteer

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 proposal: (1) Progression of the most advanced of our construct 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. (e) 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.

化脓性链球菌（Streptococcus pyogenes，GAS）是一种革兰氏阳性细菌， 引起包括相对良性的咽炎和皮肤感染在内的多种疾病的病原体 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，没有一项初级预防战略， 证明在欠发达国家有效，因此疫苗显然是必要的。根据一些疫苗战略， 发展在欠发达国家可能没有成效。我们的长期目标是发展 预防GAS感染及其相关疾病（包括风湿性关节炎）的广谱全球疫苗 发烧我们的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，每一种都表现出良好的效果 免疫原性、安全性和保护性。 本提案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 预期已完成： (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。 (e)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)在一个发展中国家进行实地研究，以确定可用于第二阶段的保护相关因素， III保守区肽的临床试验，并为这些后期试验建立现场。

项目成果

High prevalence of rheumatic heart disease by clinical and echocardiographic screening among children in Fiji.

通过临床和超声心动图筛查，斐济儿童中风湿性心脏病的患病率很高。

• 发表时间: 2009
• 期刊: The Journal of heart valve disease
• 作者: Steer,AndrewC;Kado,Joseph;Wilson,Nigel;Tuiketei,Timaima;Batzloff,Michael;Waqatakirewa,Lepani;Mulholland,EKim;Carapetis,JonathanR
• 通讯作者: Carapetis,JonathanR

Long-term antibody memory induced by synthetic peptide vaccination is protective against Streptococcus pyogenes infection and is independent of memory T cell help.

• DOI: 10.4049/jimmunol.1202333
• 发表时间: 2013-03-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Pandey M;Wykes MN;Hartas J;Good MF;Batzloff MR
• 通讯作者: Batzloff MR

Prospective surveillance of invasive group a streptococcal disease, Fiji, 2005-2007.

• DOI: 10.3201/eid1502.080558
• 发表时间: 2009-02
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Steer AC;Jenney A;Kado J;Good MF;Batzloff M;Waqatakirewa L;Mullholland EK;Carapetis JR
• 通讯作者: Carapetis JR

emm and C-repeat region molecular typing of beta-hemolytic Streptococci in a tropical country: implications for vaccine development.

热带国家 β 溶血性链球菌的 emm 和 C 重复区域分子分型：对疫苗开发的影响。

• DOI: 10.1128/jcm.00312-09
• 发表时间: 2009
• 期刊: Journal of clinical microbiology
• 影响因子: 9.4
• 作者: Steer,AndrewC;Magor,Graham;Jenney,AdamWJ;Kado,Joseph;Good,MichaelF;McMillan,David;Batzloff,Michael;Carapetis,JonathanR
• 通讯作者: Carapetis,JonathanR