Immunotherapeutics to prevent the replication of Brucella in a treatment failure mouse model.

Immunotherapeutics to prevent the replication of Brucella in a treatment failure mouse model.
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免疫疗法可防止治疗失败的小鼠模型中布鲁氏菌的复制。

DOI:
10.1016/j.vaccine.2013.12.058
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发表时间:
2014
期刊:
影响因子:
5.5
通讯作者:
Sriranganathan,N
Sriranganathan,N
中科院分区:
医学3区
文献类型:
--
作者:
Jain-Gupta,N;Contreras-Rodriguez,A;Smith,GP;Garg,VK;Witonsky,SG;Isloor,S;Vemulapalli,R;Boyle,SM;Sriranganathan,N

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羊种布氏杆菌外膜囊泡(OMV)和经辐照的新生布氏杆菌外膜囊泡(OMV)已被证明是抗aB的有效疫苗。在小鼠模型中进行的消化道激发试验。本研究评估了这两种疫苗作为免疫治疗剂与常规抗生素联合抗羊种布氏杆菌感染的疗效。BALB/c小鼠慢性感染B.用强力霉素和庆大霉素治疗4周,并在治疗过程中接种两次。选择亚治疗浓度的抗生素,使得治疗将导致小鼠治疗失败。虽然疫苗和抗生素对B.羊种球蛋白感染后,与仅用抗生素治疗的小鼠相比,接受疫苗沿着抗生素的小鼠在治疗后未表现出布鲁氏菌复制。辐照的管理。在用热灭活的dB刺激时,neotomaea和抗生素导致体外脾细胞产生更高的IFN-γ。而用OMV接种的小鼠的脾细胞没有观察到这种作用。与仅接受抗生素的小鼠相比,OMV接种的小鼠在治疗结束时产生了显著更高的抗布鲁氏菌IgG抗体滴度。与未接受疫苗的对照组小鼠相比,仅接受疫苗的小鼠没有显示出任何显着的脾脏和肝脏布鲁氏菌清除。这项研究表明,将OMV或辐照dB。在治疗失败的病例中,新瘤与常规抗生素一起使用可能能够提高治疗效果并控制疾病进展。
Outer membrane vesicles (OMVs) fromBrucella melitensisand irradiatedBrucella neotomaehave been shown to be effective vaccines against aB. melitensischallenge in a mouse model. The present study evaluates the efficacy of these two vaccines as immuno-therapeutics in combination with conventional antibiotics against aB.melitensisinfection. BALB/c mice chronically infected withB. melitensiswere 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 ofB. melitensis, mice receiving vaccines along with antibiotics exhibited noBrucellareplication post-treatment compared to mice treated only with antibiotics. Administration of irradiatedB. neotomaealong with antibiotics led to higher production of IFN-γex vivoby splenocytes upon stimulation with heat inactivatedB. melitensiswhile no such effect was seen by splenocytes from mice vaccinated with OMVs. OMV vaccinated mice developed significantly higher anti-BrucellaIgG 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 ofBrucellafrom spleens and livers compared to non-treated control mice. This study suggests that incorporating OMVs or irradiatedB. neotomaealong with conventional antibiotics might be able to improve therapeutic efficacy and control the progression of disease in treatment failure cases.