The Effects of Vaccination and Immunity on Bacterial Infection Dynamics In Vivo

PLoS Pathogens

Chris Coward¹  Andrew J. Grant¹  Pietro Mastroeni¹  Duncan J. Maskell¹  Richard Dybowski¹  Olivier Restif¹ 

[1] University of Cambridge, Department of Veterinary Medicine, Cambridge, United Kingdom

关键词: Spleen;    T cells;    Vaccines;    Blood;    Liver;    Salmonellosis;    Salmonella;    Immune response;   

DOI  :  10.1371/journal.ppat.1004359

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY