The effects of vaccination and immunity on bacterial infection dynamics in vivo.
The effects of vaccination and immunity on bacterial infection dynamics in vivo.
复制标题
DOI：
10.1371/journal.ppat.1004359
复制
发表时间：
2014-09
期刊：
影响因子：
6.7
通讯作者：
Mastroeni P
中科院分区：
文献类型：
--
作者：
Coward C;Restif O;Dybowski R;Grant AJ;Maskell DJ;Mastroeni P
肠道沙门氏菌感染是一个重要的全球健康问题，针对这些细菌的疫苗的开发需要更好地了解疫苗接种如何影响宿主内细菌的生长和传播。我们结合了分子标记的细菌亚群的体内跟踪与数学建模，以获得不同类别的疫苗和免疫反应的分支如何防止小鼠继发性肠道沙门氏菌感染的新见解。我们已经发现，活沙门氏菌疫苗显着减少菌血症在二次挑战和抑制器官间传播的细菌在全身器官。此外，将机理模型与数据拟合表明，活疫苗免疫增强了感染早期阶段的细菌杀灭和攻毒后第一天的抑菌控制。由该疫苗诱导的T细胞免疫对于增强抑菌作用不是必需的，但对于随后的血液和组织中沙门氏菌的杀菌清除是必需的。相反，非活疫苗虽然能够提高初始血液清除率并杀死毒性二次攻击细菌，但无法改变随后全身器官中的细菌生长速率，不能防止广泛菌血症的复发，也不能控制细菌在体内的传播。肠道沙门氏菌引起胃肠炎和严重的全身性疾病伤寒、副伤寒和非伤寒败血症（NTS）。由于获得耐药性，用抗生素治疗全身性疾病变得越来越困难。有许可的疫苗可用于预防伤寒，但不包括副伤寒或NTS。疫苗可以是活的（减毒菌株）或非活的（例如灭活的全细胞或表面多糖），这些不同的类别可能激活宿主免疫系统的不同组分。疫苗设计的改进需要更好地了解不同类型的疫苗在控制随后感染的能力方面的差异。我们改进了先前开发的实验系统和数学模型，以研究这些不同类型的疫苗如何发挥作用。我们表明，灭活疫苗只能通过杀菌活性的短暂增加来控制细菌数量，而活疫苗是上级的，因为它可以诱导免疫应答，快速杀死，然后抑制感染细菌的生长和传播。
Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body. The bacterium Salmonella enterica causes gastroenteritis and the severe systemic diseases typhoid, paratyphoid fever and non-typhoidal septicaemia (NTS). Treatment of systemic disease with antibiotics is becoming increasingly difficult due to the acquisition of resistance. Licensed vaccines are available for the prevention of typhoid, but not paratyphoid fever or NTS. Vaccines can be either living (attenuated strains) or non-living (e.g. inactivated whole cells or surface polysaccharides) and these different classes potentially activate different components of the host immune system. Improvements in vaccine design require a better understanding of how different vaccine types differ in their ability to control a subsequent infection. We have improved a previously developed experimental system and mathematical model to investigate how these different vaccine types act. We show that the inactivated vaccine can only control bacterial numbers by a transient increase in bactericidal activity whereas the living vaccine is superior as it can induce an immune response that rapidly kills, then restrains the growth and spread of infecting bacteria.
登录
查看更多内容
影响因子：
9.8
作者：
Grant AJ;Restif O;McKinley TJ;Sheppard M;Maskell DJ;Mastroeni P
通讯作者：
Mastroeni P
影响因子：
11.8
作者：
Hohmann, EL
通讯作者：
Hohmann, EL
影响因子：
6.2
作者：
Layton, Abigail N.;Galyov, Edouard E.
通讯作者：
Galyov, Edouard E.
影响因子：
15.3
作者：
MACKANESS, GB;BLANDEN, RV;COLLINS, FM
通讯作者：
COLLINS, FM
通过巨噬细胞对沙门氏菌的内在化会导致形成非复制的持久性。
DOI：
10.1126/science.1244705
发表时间：
2014-01-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Helaine S;Cheverton AM;Watson KG;Faure LM;Matthews SA;Holden DW
通讯作者：
Holden DW