title: Immunotherapeutics to prevent the replication of Brucella in a treatment failure mouse model.
abstract: Outer membrane vesicles (OMVs) from Brucella melitensis and irradiated Brucella neotomae have been shown to be effective vaccines against a B. melitensis challenge in a mouse model. The present study evaluates the efficacy of these two vaccines as immuno-therapeutics in combination with conventional antibiotics against a B. melitensis infection. BALB/c mice chronically infected with B. melitensis were treated for 4 weeks with doxycycline and gentamicin and vaccinated twice during the course of therapy. Antibiotics in sub-therapeutic concentrations were chosen in such a way that the treatment would result in a therapeutic failure in mice. Although no additive effect of vaccines and antibiotics was seen on the clearance of B. melitensis, mice receiving vaccines along with antibiotics exhibited no Brucella replication post-treatment compared to mice treated only with antibiotics. Administration of irradiated B. neotomae along with antibiotics led to higher production of IFN-γ ex vivo by splenocytes upon stimulation with heat inactivated B. melitensis while no such effect was seen by splenocytes from mice vaccinated with OMVs. OMV vaccinated mice developed significantly higher anti-Brucella IgG antibody titers at the end of the treatment compared to the mice that received only antibiotics. The mice that received only vaccines did not show any significant clearance of Brucella from spleens and livers compared to non-treated control mice. This study suggests that incorporating OMVs or irradiated B. neotomae along with conventional antibiotics might be able to improve therapeutic efficacy and control the progression of disease in treatment failure cases.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0342, United States.
authors.forename: N
authors.initials: N
authors.lastname: Jain-Gupta
authors.affiliation: Departmento de Microbiologia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Contreras-Rodriguez
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0342, United States.
authors.forename: G P
authors.initials: GP
authors.lastname: Smith
authors.affiliation: Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, United States.
authors.forename: V K
authors.initials: VK
authors.lastname: Garg
authors.affiliation: Department of Large Animal Clinical Sciences, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0342, United States.
authors.forename: S G
authors.initials: SG
authors.lastname: Witonsky
authors.affiliation: Department of Veterinary Microbiology, Veterinary College, Karnataka Veterinary, Animal Sciences and Fisheries University, Hebbal, Bangalore 560024, India.
authors.forename: S
authors.initials: S
authors.lastname: Isloor
authors.affiliation: Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, United States.
authors.forename: R
authors.initials: R
authors.lastname: Vemulapalli
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0342, United States.
authors.forename: S M
authors.initials: SM
authors.lastname: Boyle
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0342, United States. Electronic address: nathans@vt.edu.
authors.forename: N
authors.initials: N
authors.lastname: Sriranganathan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002002:Brucella; D002004:Brucella Vaccine / Q000627:therapeutic use*; D017347:Brucella melitensis / Q000472:pathogenicity*; D002006:Brucellosis / Q000517:prevention & control* / Q000628:therapy*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000627:therapeutic use; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002004:Brucella Vaccine; D005839:Gentamicins; D007074:Immunoglobulin G; D007371:Interferon-gamma; D004318:Doxycycline
keywords: Brucellosis; Cell mediated immunity and humoral immunity; Immunotherapy; Outer membrane vesicles; Therapeutic vaccine; Treatment failure