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.
Departmento de Microbiologia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico.
Vaccine. 2014 Feb 12;32(8):918-23. doi: 10.1016/j.vaccine.2013.12.058. Epub 2014 Jan 4.
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.
从绵羊布鲁氏菌和辐照新托马斯布鲁氏菌中提取的外膜囊泡（OMVs）已被证明可有效预防小鼠模型中绵羊布鲁氏菌的攻击。本研究评估了这两种疫苗作为免疫疗法与常规抗生素联合使用对绵羊布鲁氏菌感染的疗效。用多西环素和庆大霉素治疗慢性感染绵羊布鲁氏菌的 BALB/c 小鼠 4 周，并在治疗过程中进行两次疫苗接种。选择亚治疗浓度的抗生素，以使治疗导致小鼠治疗失败。尽管疫苗和抗生素联合使用对清除绵羊布鲁氏菌没有叠加作用，但与仅用抗生素治疗的小鼠相比，接受疫苗和抗生素治疗的小鼠在治疗后没有布鲁氏菌复制。与用 OMVs 接种的小鼠相比，在用抗生素联合辐照新托马斯布鲁氏菌给药后，脾细胞在用灭活的绵羊布鲁氏菌刺激时产生更高水平的 IFN-γ。用 OMV 接种的小鼠在治疗结束时比仅用抗生素治疗的小鼠产生更高的抗布鲁氏菌 IgG 抗体滴度。与未治疗的对照小鼠相比，仅接受疫苗的小鼠脾脏和肝脏中布鲁氏菌的清除没有任何显著改善。本研究表明，将 OMVs 或辐照新托马斯布鲁氏菌与常规抗生素联合使用可能能够提高治疗效果并控制治疗失败病例中疾病的进展。
