Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice w...Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens （SLA） alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin （BCG） vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin （IL）-4, IL-5 and gamma interferon （IFN-γ） determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results： Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 （P 〈 0.05） and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA ＋ artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice （P 〉 0.05）, resulting in exacerbated disease. Conclusion： These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.展开更多
Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-...Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-11 antigen through murine dendritic cells against VL in infected BALB/c mice. We report here that immunization with KMP-11 delivered through bone marrow derived dendritic cells can lead to killing of L. donovani in infected BALB/c mice. Furthermore, the strategy to use KMP-11 as vaccine delivered through DCs can stimulate the production of IFN-g, IL-12, IL-2R and TNF-α with concomitant down-regulation of IL-10 and IL-4. Furthermore, anti-leishmanial defence function (ROS) of splenocytes was observed increased in the presence of DC-delivered KMP-11 vaccination accompanied with an increased p38-MAPK signalling in vaccinated splenocytes. We summarized from our data that KMP-11 delivered through DCs has potential for eliciting protective immunity through pro-inflammatory cytokines (IFN-γ, IL-12, IL-2, TNF-α) following an up-regulation in signalling event of p38-MAPK. Therefore the study suggests a new control strategy against VL in future.展开更多
文摘Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens （SLA） alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin （BCG） vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin （IL）-4, IL-5 and gamma interferon （IFN-γ） determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results： Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 （P 〈 0.05） and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA ＋ artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice （P 〉 0.05）, resulting in exacerbated disease. Conclusion： These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.
文摘Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-11 antigen through murine dendritic cells against VL in infected BALB/c mice. We report here that immunization with KMP-11 delivered through bone marrow derived dendritic cells can lead to killing of L. donovani in infected BALB/c mice. Furthermore, the strategy to use KMP-11 as vaccine delivered through DCs can stimulate the production of IFN-g, IL-12, IL-2R and TNF-α with concomitant down-regulation of IL-10 and IL-4. Furthermore, anti-leishmanial defence function (ROS) of splenocytes was observed increased in the presence of DC-delivered KMP-11 vaccination accompanied with an increased p38-MAPK signalling in vaccinated splenocytes. We summarized from our data that KMP-11 delivered through DCs has potential for eliciting protective immunity through pro-inflammatory cytokines (IFN-γ, IL-12, IL-2, TNF-α) following an up-regulation in signalling event of p38-MAPK. Therefore the study suggests a new control strategy against VL in future.
