原创力文档cell-associated flagella enhance the protection conferred by mucosally-administered attenuated salmonella paratyphi a vaccines细胞相关鞭毛增强赋予的保护mucosally-administered减毒甲型副伤寒沙门氏菌疫苗.pdfVIP
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cell-associated flagella enhance the protection conferred by mucosally-administered attenuated salmonella paratyphi a vaccines细胞相关鞭毛增强赋予的保护mucosally-administered减毒甲型副伤寒沙门氏菌疫苗
Cell-Associated Flagella Enhance the Protection
Conferred by Mucosally-Administered Attenuated
Salmonella Paratyphi A Vaccines
Orit Gat1,2, James E. Galen1,2*, Sharon Tennant1,2, Raphael Simon1,2, William C. Blackwelder1,2, David J.
Silverman3, Marcela F. Pasetti1,4, Myron M. Levine1,2,4
1 Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 2 Department of Medicine, University of
Maryland School of Medicine, Baltimore, Maryland, United States of America, 3 Department of Microbiology and Immunology, University of Maryland School of Medicine,
Baltimore, Maryland, United States of America, 4 Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
Abstract
Background: Antibiotic-resistant Salmonella enterica serovar Paratyphi A, the agent of paratyphoid A fever, poses an
emerging public health dilemma in endemic areas of Asia and among travelers, as there is no licensed vaccine. Integral to
our efforts to develop a S. Paratyphi A vaccine, we addressed the role of flagella as a potential protective antigen by
comparing cell-associated flagella with exported flagellin subunits expressed by attenuated strains.
Methodology: S. Paratyphi A strain ATCC 9150 was first deleted for the chromosomal guaBA locus, creating CVD 1901.
Further chromosomal deletions in fliD (CVD 1901D) or flgK (CVD 1901K) were then engineered, resulting in the export of
unpolymerized FliC, without impairing its overall expression. The virulence of the resulting isogenic strains was examined
using a novel mouse LD50 model to accommodate the human-host restricted S. Paratyphi A. The immunogenicity of the
attenuated strains was then tested using a mouse intranasal model, followed by intraperitoneal challenge with wildtype
ATCC 9150.
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