Live Attenuated Human Salmonella Vaccine Candidates: Tracking the Pathogen in Natural Infection and Stimulation of Host Immunity

Author:

Galen James E.12,Buskirk Amanda D.34,Tennant Sharon M.32,Pasetti Marcela F.34

Affiliation:

1. Center for Vaccine Development, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD 21201

2. Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201

3. Center for Vaccine Development, Institute for Global Health, University of Maryland School of Medicine, Baltimore MD 21201

4. Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201

Abstract

Salmonellosis, caused by members of the genus Salmonella , is responsible for considerable global morbidity and mortality in both animals and humans. In this review, we will discuss the pathogenesis of Salmonella enterica serovar Typhi and Salmonella enterica serovar Typhimurium, focusing on human Salmonella infections. We will trace the path of Salmonella through the body, including host entry sites, tissues and organs affected, and mechanisms involved in both pathogenesis and stimulation of host immunity. Careful consideration of the natural progression of disease provides an important context in which attenuated live oral vaccines can be rationally designed and developed. With this in mind, we will describe a series of attenuated live oral vaccines that have been successfully tested in clinical trials and demonstrated to be both safe and highly immunogenic. The attenuation strategies summarized in this review offer important insights into further development of attenuated vaccines against other Salmonella for which live oral candidates are currently unavailable.

Publisher

American Society for Microbiology

Subject

Microbiology

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