A Highly Effective Component Vaccine against Nontyphoidal Salmonella enterica Infections.
A Highly Effective Component Vaccine against Nontyphoidal Salmonella enterica Infections.
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DOI：
10.1128/mbio.01421-15
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发表时间：
2015-09-22
期刊：
影响因子：
6.4
通讯作者：
Finlay BB
中科院分区：
文献类型：
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作者：
Ferreira RB;Valdez Y;Coombes BK;Sad S;Gouw JW;Brown EM;Li Y;Grassl GA;Antunes LC;Gill N;Truong M;Scholz R;Reynolds LA;Krishnan L;Zafer AA;Sal-Man N;Lowden MJ;Auweter SD;Foster LJ;Finlay BB
非伤寒性肠道沙门氏菌（NTS）感染是全球公共卫生的主要负担，因为它们导致从胃肠炎到全身感染的疾病，并且目前没有可用的疫苗。在这里，我们描述了一种针对沙门氏菌的高效成分疫苗。肠血清型鼠伤寒沙门氏菌在胃肠炎和全身性鼠感染模型中的作用。我们设计了一种产生S.肠血清型鼠伤寒沙门氏菌，一种毒力因子高度丰富的生物体。用该上清液免疫小鼠导致对鼠伤寒血清型攻击的显著保护，显示在全身模型中存活率增加和在胃肠道模型中肠道病理学减少。保护与免疫小鼠血清中特异性伊加和IgG水平和粪便中特异性分泌伊加水平相关。细菌培养物上清液中保护性抗原的初步表征揭示了一个抗原亚组，其表现出显著的稳定性，这是在发展中国家次优环境条件下使用的有效疫苗的非常理想的特征。我们能够纯化存在于上清液中的肽的子集，并显示它们对鼠伤寒血清型免疫小鼠的潜力，导致定殖水平降低。该疫苗组分在预防NTS方面显示出希望，并且进一步的工作将显著有助于建立针对这些流行感染的疫苗。伤寒和副伤寒以外的肠道沙门氏菌感染是一个主要的全球健康负担，因为它们在世界范围内引起高发病率和死亡率。非常需要预防沙门氏菌相关疾病的策略，并且大力推动针对非伤寒沙门氏菌血清型的疫苗的开发。在这项工作中，我们描述了一种鼠伤寒沙门氏菌上清液衍生的疫苗，有效地减少胃肠炎以及侵袭性疾病的小鼠模型中的细菌定植。这是一种对热具有高度稳定性的组分疫苗，这一特征对于在次优条件下使用非常重要，例如在撒哈拉以南非洲发现的那些条件。
Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica serovar Typhimurium in both gastroenteritis and systemic murine infection models. We devised an approach to generate supernatants of S. enterica serovar Typhimurium, an organism that is highly abundant in virulence factors. Immunization of mice with this supernatant resulted in dramatic protection against a challenge with serovar Typhimurium, showing increased survival in the systemic model and decreased intestinal pathology in the gastrointestinal model. Protection correlated with specific IgA and IgG levels in the serum and specific secretory IgA levels in the feces of immunized mice. Initial characterization of the protective antigens in the bacterial culture supernatants revealed a subset of antigens that exhibited remarkable stability, a highly desirable characteristic of an effective vaccine to be used under suboptimal environmental conditions in developing countries. We were able to purify a subset of the peptides present in the supernatants and show their potential for immunization of mice against serovar Typhimurium resulting in a decreased level of colonization. This component vaccine shows promise with regard to protecting against NTS, and further work should significantly help to establish vaccines against these prevalent infections. Salmonella enterica infections other than typhoid and paratyphoid fever are a major global health burden, as they cause high morbidity and mortality worldwide. Strategies that prevent Salmonella-related diseases are greatly needed, and there is a significant push for the development of vaccines against nontyphoidal Salmonella enterica serovars. In this work, we describe an S. Typhimurium supernatant-derived vaccine that is effective in reducing bacterial colonization in mouse models of gastroenteritis as well as invasive disease. This is a component vaccine that shows high stability to heat, a feature that is important for use under suboptimal conditions, such as those found in sub-Saharan Africa.