title: Live Brucella abortus rough vaccine strain RB51 stimulates enhanced innate immune response in vitro compared to rough vaccine strain RB51SOD and virulent smooth strain 2308 in murine bone marrow-derived dendritic cells.
abstract: Brucella spp. are Gram-negative, coccobacillary, facultative intracellular pathogens. B. abortus strain 2308 is a pathogenic strain affecting cattle and humans. Rough B. abortus strain RB51, which lacks the O-side chain of lipopolysaccharide (LPS), is the live attenuated USDA approved vaccine for cattle in the United States. Strain RB51SOD, which overexpresses Cu-Zn superoxide dismutase (SOD), has been shown to confer better protection than strain RB51 in a murine model. Protection against brucellosis is mediated by a strong CD4+ Th(1) and CD8+ Tc(1) adaptive immune response. In order to stimulate a robust adaptive response, a solid innate immune response, including that mediated by dendritic cells, is essential. As dendritic cells (DCs) are highly susceptible to Brucella infection, it is possible that pathogenic strains could limit the innate and thereby adaptive immune response. By contrast, vaccine strains could limit or bolster the innate and subsequent adaptive immune response. Identifying how Brucella vaccines stimulate innate and adaptive immunity is critical for enhancing vaccine efficacy. The ability of rough vaccine strains RB51 and RB51SOD to stimulate DC function has not been characterized. We report that live rough vaccine strain RB51 induced significantly better (p ≤ 0.05) DC maturation and function compared to either strain RB51SOD or smooth virulent strain 2308, based on costimulatory marker expression and cytokine production.
authors.affiliation: Department of Large Animal Clinical Sciences, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0342, USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Surendran
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hiltbold
authors.forename: Bettina
authors.initials: B
authors.lastname: Heid
authors.forename: Nammalwar
authors.initials: N
authors.lastname: Sriranganathan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Boyle
authors.forename: Kurt L
authors.initials: KL
authors.lastname: Zimmerman
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Makris
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Witonsky
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000382:microbiology; D002004:Brucella Vaccine / Q000276:immunology*; D002003:Brucella abortus / Q000276:immunology*; D002007:Brucellosis, Bovine / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002417:Cattle; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014481:United States
chemical_list: D051940:B7-2 Antigen; D002004:Brucella Vaccine; D019013:CD40 Antigens; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12