title: Protection to respiratory challenge of Brucella abortus strain 2308 in the lung.
abstract: Brucella is amongst the top 5 causes of zoonotic disease worldwide. Infection is through ingestion, inhalation or contact exposure. Brucella is characterized as a class B pathogen by Centers of Disease Control and Prevention (CDC). Currently, there are no efficacious vaccines available in people. Currently available USDA approved vaccines for animals include B. abortus strain RB51 and B. melitensis Rev1. Protection is mediated by a strong innate and CD4 Th1, CD8 Tc1 immune response. If protective vaccines can be developed, disease in people and animals can be controlled. While strain RB51 protects in cattle, and against intraperitoneal challenge in mice, it does not protect against respiratory challenge. Therefore, we assessed the efficacy of strain RB51 combined with different TLR agonists, and O-side chain from LPS, to enhance protection against respiratory challenge with strain 2308. We hypothesized that TLR agonists and O-side chain would enhance protection. Strains RB51 with TLR2 agonist, RB51 with TLR4 agonist and strain 19 provided significant protection in the lung. Protection using strain RB51 with TLR agonists was associated with increased IgG2a and IgG1 in the (bronchoalveolar lavage) BAL and serum, and increased IgA (serum). Splenocytes from strain RB51 with TLR2 vaccinated mice up-regulated antigen specific interferon-gamma and TNF-alpha production. Vaccination and challenge resulted in significant increases in activated dendritic cells (DCs), and increased CD4 and CD8 cells in the BAL. Overall, this study demonstrates the ability of TLR agonists 2 and 4 to up-regulate strain RB51 mediated protection in the lung to respiratory challenge against strain 2308.
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: Nammalwar
authors.initials: N
authors.lastname: Sriranganathan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Boyle
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hiltbold
authors.forename: Nancy
authors.initials: N
authors.lastname: Tenpenny
authors.forename: Michelle
authors.initials: M
authors.lastname: Walker
authors.forename: Kurt
authors.initials: K
authors.lastname: Zimmerman
authors.forename: Stephen
authors.initials: S
authors.lastname: Werre
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Witonsky
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002004:Brucella Vaccine / Q000494:pharmacology*; D002003:Brucella abortus / Q000472:pathogenicity*; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D039001:Integrin alpha Chains / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051217:Toll-Like Receptor 9 / Q000819:agonists
chemical_list: D015703:Antigens, CD; D002004:Brucella Vaccine; D039481:CD11b Antigen; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D039001:Integrin alpha Chains; D020381:Interleukin-17; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C091367:alpha E integrins
keywords: Brucella; Dendritic cell; Respiratory