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.
复制标题
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
复制
发表时间:
2014
期刊:
影响因子:
5.5
通讯作者:
Sriranganathan,N
中科院分区:
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
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.