Live Attenuated Human Salmonella Vaccine Candidates: Tracking the Pathogen in Natural Infection and Stimulation of Host Immunity.
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.
Center for Vaccine Development, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD 21201.
James E
JE
Galen
Center for Vaccine Development, Institute for Global Health, University of Maryland School of Medicine, Baltimore MD 21201.
Amanda D
AD
Buskirk
Center for Vaccine Development, Institute for Global Health, University of Maryland School of Medicine, Baltimore MD 21201.
Sharon M
SM
Tennant
Center for Vaccine Development, Institute for Global Health, University of Maryland School of Medicine, Baltimore MD 21201.
Marcela F
MF
Pasetti
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D000071497:Immunogenicity, Vaccine; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology*; D012481:Salmonella Infections, Animal; D022562:Salmonella Vaccines / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology* / Q000472:pathogenicity; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity; D065288:Serogroup; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
D000907:Antibodies, Bacterial; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated