Antibodies and protection against invasive salmonella disease.

Calman A Maclennan

doi:10.3389/fimmu.2014.00635

Abstract

Invasive disease caused by Salmonella enterica is a major global public health concern. It has two main clinical forms: enteric fever and invasive nontyphoidal Salmonella (iNTS) disease. Enteric fever imposes its highest burden of disease in South and South-East Asia and is principally caused by S. Typhi and S. Paratyphi A. Conversely, iNTS disease is a particular problem in sub-Saharan Africa where it is a leading cause of bacteremia (1, 2) and is mainly caused by S. Typhimurium and S. Enteritidis. As facultative intracellular bacteria, Salmonellae persist and multiply within the intracellular niche in macrophages but they are also capable of independent cell-free existence and this enables the spread of the infection from macrophage to macrophage. The way the immune system protects against these two phases of infection differs and this is key for developing a strategy to induce protective immunity against Salmonella. Antibodies have an important role in eliminating extracellular bacteria, while specific T cells are important for the clearance of intracellular bacteria. The contribution of these two arms of acquired immunity against Salmonella infections to protection has been an area of controversy in the past, and their relative importance is only now emerging. This opinion piece focuses on the role of antibodies in protecting against invasive Salmonella disease, and the application of this to vaccine development.

Highlights

Epidemiological investigation, in vitro studies, animal models and vaccine studies indicate that antibodies can kill Salmonella that are not shielded by residing inside host cells
An important consideration is the time that these bacteria are exposed to antibodies and whether this is sufficient for antibodyinduced killing to occur
Typhimurium are killed by antibody and complement, and this time is sufficient to allow a proportion of bacteria entering the blood to escape into the intracellular niche [4]

Summary

Introduction

Epidemiological investigation, in vitro studies, animal models and vaccine studies indicate that antibodies can kill Salmonella that are not shielded by residing inside host cells. Candidate vaccine studies in mice, where immunization is followed by challenge with live Salmonella, indicate the importance of antibodies for protection. There is evidence regarding the mechanisms of immune protection from vaccines against typhoid fever, no vaccine against NTS has progressed beyond a phase I clinical study.

Results

Conclusion