StreptInCor:一种抗化脓性链球菌疫苗的模型综述。

Q1 Medicine Auto-Immunity Highlights Pub Date : 2013-10-04 eCollection Date: 2013-12-01 DOI:10.1007/s13317-013-0053-8
Luiza Guilherme, Edilberto Postol, Frederico Moraes Ferreira, Lea M F DeMarchi, Jorge Kalil
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引用次数: 6

摘要

化脓性链球菌感染在许多国家仍然是一个健康问题,因为产后后遗症,如风湿热和风湿性心脏病。不发达国家和发展中国家链球菌疾病的流行病学增长鼓励许多团体研究预防A组链球菌感染的候选疫苗。我们开发了一种疫苗表位(StreptInCor),由M蛋白C末端的55个氨基酸残基组成,包括T和B细胞保护性表位。使用人类血液样本,我们发现StreptInCor表位被携带不同HLA II类分子的个体识别,可以被认为是一种通用的疫苗表位。此外,通过核磁共振波谱对StreptInCor分子结构进行了求解,并进行了一系列结构稳定性实验来阐明其折叠/展开机制。使用BALB-c和HLA II类转基因小鼠,我们评估了长期的免疫反应,发现StreptInCor能够在两种模型中诱导强大的免疫反应。未观察到针对心脏蛋白质的交叉反应。通过分析组织病理学来评估疫苗表位的安全性,在心脏或其他器官中没有观察到自身免疫或病理反应。用化脓性链球菌强毒株攻击的接种疫苗的BALB/c小鼠在30天内具有100%的存活率。综合考虑所有结果,StreptInCor可能是一种安全有效的抗链球菌诱导疾病的疫苗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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StreptInCor: a model of anti-Streptococcus pyogenes vaccine reviewed.

Streptococcus pyogenes infections remain a health problem in multiple countries because of poststreptococcal sequelae, such as rheumatic fever and rheumatic heart disease. The epidemiological growth of streptococcal diseases in undeveloped and developing countries has encouraged many groups to study vaccine candidates for preventing group A streptococcus infections. We developed a vaccine epitope (StreptInCor) composed of 55 amino acid residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. Using human blood samples, we showed that the StreptInCor epitope is recognized by individuals bearing different HLA class II molecules and could be considered a universal vaccine epitope. In addition, the StreptInCor molecular structure was solved by nuclear magnetic resonance spectroscopy, and a series of structural stability experiments was performed to elucidate its folding/unfolding mechanism. Using BALB-c and HLA class II transgenic mice, we evaluated the immune response over an extended period and found that StreptInCor was able to induce a robust immune response in both models. No cross-reaction was observed against cardiac proteins. The safety of the vaccine epitope was evaluated by analyzing histopathology, and no autoimmune or pathological reactions were observed in the heart or other organs. Vaccinated BALB/c mice challenged with a virulent strain of S. pyogenes had 100 % survival over 30 days. Taking all results into account, StreptInCor could be a safe and effective vaccine against streptococcus-induced disease.

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