Journal
VACCINE
Volume 32, Issue 8, Pages 918-923Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2013.12.058
Keywords
Brucellosis; Treatment failure; Immunotherapy; Therapeutic vaccine; Outer membrane vesicles; Cell mediated immunity and humoral immunity
Categories
Funding
- National Institute of Allergy and Infectious Diseases [AI065667-01A2]
- Virginia Tech Institute for Critical Technology and Applied Sciences (ICTAS) [AI065667-01A2]
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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-gamma 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. (C) 2014 Elsevier Ltd. All rights reserved.
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