title: Heterologous Pseudomonas aeruginosa O-antigen delivery using a Salmonella enterica serovar Typhimurium wecA mutant strain.
abstract: There is a broad interest in adapting live vaccine strains (LVS) for use as recombinant vaccines that can deliver heterologous antigens. The Salmonella enterica serovar Typhimurium SL1344 ΔwecA LVS contains a mutation in wecA that abrogates production of Enterobacterial common antigen. This ΔwecA strain is attenuated in vivo, persistently colonizes the host, and protects against both wild type and cross-Salmonella serovar lethal challenge in a murine model of salmonellosis. Given these characteristics, we hypothesized that the SL1344 ΔwecA strain could be used as a carrier for heterologous antigen expression. To test this hypothesis, SL1344 ΔwecA was engineered to express the Pseudomonas aeruginosa O11 O-antigen gene cluster. Intraperitoneal (IP) but not oral immunization of BALB/c mice with the heterologous expression strain protected against lethal P. aeruginosa intranasal (IN) challenge. Furthermore, IP immunization resulted in P. aeruginosa O11-specific Ig and IgG antibody production. Functional analysis of sera collected from the IP immunized mice showed antibody-mediated agglutination and opsonophagocytic activity against P. aeruginosa. En masse, these results indicate that the S. Typhimurium SL1344 ΔwecA strain expressing the P. aeruginosa O11 O-antigen gene cluster is able to induce a humoral immune response and to protect against lethal P. aeruginosa challenge. As such, the S. Typhimurium SL1344 ΔwecA LVS can likely serve as a vehicle for expression of a wide variety of heterologous antigens as a means to create recombinant vaccines.
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States. Electronic address: dacie.bridge.ctr@usuhs.edu.
authors.forename: Dacie R
authors.initials: DR
authors.lastname: Bridge
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States. Electronic address: jeannette.whitmire@usuhs.edu.
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Whitmire
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States. Electronic address: Morris.Makobongo@uscmed.sc.edu.
authors.forename: Morris O
authors.initials: MO
authors.lastname: Makobongo
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States. Electronic address: douglas.merrell@usuhs.edu.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Merrell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D007274:Injections, Intraperitoneal; D008807:Mice, Inbred BALB C; D019081:O Antigens / Q000235:genetics* / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000235:genetics*; D012486:Salmonella typhimurium / Q000235:genetics*; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D004337:Drug Carriers; D019081:O Antigens; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
keywords: Heterologous antigen presentation; Live-attenuated; Pseudomonas aeruginosa; Salmonella Typhimurium; Vaccine; wecA