The effects of vaccination and immunity on bacterial infection dynamics in vivo.

Denise M Monack,Chris Coward,Olivier Restif,Andrew J Grant,Pietro Mastroeni,Richard Dybowski,Duncan J Maskell

doi:10.1371/journal.ppat.1004359

Abstract

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.

Highlights

IntroductionSalmonella enterica causes systemic diseases (typhoid and paratyphoid fever) [1], food-borne gastroenteritis and nontyphoidal septicaemia (NTS) [2,3,4] in humans and in many other animal species world-wide
Salmonella enterica causes systemic diseases [1], food-borne gastroenteritis and nontyphoidal septicaemia (NTS) [2,3,4] in humans and in many other animal species world-wide
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, restrains the growth and spread of infecting bacteria

Summary

Introduction

Salmonella enterica causes systemic diseases (typhoid and paratyphoid fever) [1], food-borne gastroenteritis and nontyphoidal septicaemia (NTS) [2,3,4] in humans and in many other animal species world-wide. To attain a high level of protective immunity against systemic infections with virulent strains of Salmonella in susceptible hosts it is necessary to induce both antibody responses and T-helper type 1 (TH1) cell-mediated immunity [8]. This is due to the fact that intracellular control requires TH1 immunity whereas antibodies can only target the bacteria in the extracellular compartment (reviewed in [9,10])

Methods

Results

Discussion

Conclusion