title: Attenuating gene expression (AGE) for vaccine development.
abstract: Live attenuated vaccines are adept in stimulating protective immunity. Methods for generating such vaccines have largely adopted strategies used with Salmonella enterica. Yet, when similar strategies were tested in other gram-negative bacteria, the virulence factors or genes responsible to incapacitate Salmonella often failed in providing the desired outcome. Consequently, conventional live vaccines rely on prior knowledge of the pathogen's virulence factors to successfully attenuate them. This can be problematic since such bacterial pathogens normally harbor thousands of genes. To circumvent this problem, we found that overexpression of bacterial appendages, e.g., fimbriae, capsule, and flagella, could successfully attenuate wild-type (wt) Salmonella enterica serovar Typhimurium. Further analysis revealed these attenuated Salmonella strains conferred protection against wt S. Typhimurium challenge as effectively as genetically defined Salmonella vaccines. We refer to this strategy as attenuating gene expression (AGE), a simple efficient approach in attenuating bacterial pathogens, greatly facilitating the construction of live vaccines.
authors: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL USA. pascuald@ufl.edu
authors: David W
authors: DW
authors: Pascual
authors: Zhiyong
authors: Z
authors: Suo
authors: Ling
authors: L
authors: Cao
authors: Recep
authors: R
authors: Avci
authors: Xinghong
authors: X
authors: Yang
mesh_terms: D000818:Animals; D015870:Gene Expression; D006801:Humans; D015388:Organelles / Q000235:genetics / Q000276:immunology; D022562:Salmonella Vaccines / Q000235:genetics* / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000472:pathogenicity*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D037521:Virulence Factors
keywords: CFA/I fimbriae; F1 capsule; Salmonella; appendages; attenuating gene expression (AGE); flagella; vaccine
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