AIM： To construct the recombinant Lactococcus/actis as oral delivery vaccination against malaria. METHODS： The C-terminal 19-ku fragments of MSP1 （MSP-119） of Plasmodium yoelii265-BY was expressed in L. lactis and...AIM： To construct the recombinant Lactococcus/actis as oral delivery vaccination against malaria. METHODS： The C-terminal 19-ku fragments of MSP1 （MSP-119） of Plasmodium yoelii265-BY was expressed in L. lactis and the recombinant L. lact/s was administered orally to BALB/c and C57BL/6 mice. After seven interval vaccinations within 4 wk, the mice were challenged with P. yoelii 265-BY parasites of erythroo/tic stage. The protective efficacy of recombinant L. lactiswas evaluated. RESULTS： The peak parasitemias in average for the experiment groups of BALB/c and C57BL/6 mice were 0.8± 0.4% and 20.8±26.5%, respectively, and those of their control groups were 12.0±0.8% and 60.8±9.6%, respectively. None of the BALB/c mice in both experimental group and control group died during the experiment. However, all the C57BL/6 mice in the control group died within 23 d and all the vaccinated mice survived well. CONCLUSION： The results imply the potential of recombinant L. lactis as oral delivery vaccination against malaria.展开更多
Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mecha- nism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting th...Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mecha- nism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting the understanding of pathogenesis of many bacterial, fungal and protozoan pathogens and therefore the development of novel drugs and vaccines. In the most severe malaria parasite, Plasrnodiurn falciparum, there is a major virulence gene family termed vat, by which the variant antigen PfEMP1 is encoded and expressed on the surface of parasite-infected erythrocytes. Each parasite carries about 60 anti- genically various vat genes, however, only one of which is expressed at a given time during infection. P. falciparum expresses PfEMP1s in this clonally variant manner to bind to different human endothelial re- ceptors, allowing the infected erythrocytes to sequester in tissues to escape the host＇s immune response in- cluding spleen killing and humoral immunity. At present, the mechanism of mutually exclusive expression of the var gene family remains largely unknown, even though there is increasing evidence suggesting im- portant roles of the epigenetic regulation involved in vat gene expression. In addition, epigenetic factors were also found in association with transcriptional regulation of other antigenic variant gene families in P. falciparum. In this paper, we review the current understanding of epigenetic regulations of P. falcipa- rum virulence genes with particular views toward the design of novel vaccines, drugs, and diagnosis to ma- laria.展开更多
基金Supported by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), No.980198
文摘AIM： To construct the recombinant Lactococcus/actis as oral delivery vaccination against malaria. METHODS： The C-terminal 19-ku fragments of MSP1 （MSP-119） of Plasmodium yoelii265-BY was expressed in L. lactis and the recombinant L. lact/s was administered orally to BALB/c and C57BL/6 mice. After seven interval vaccinations within 4 wk, the mice were challenged with P. yoelii 265-BY parasites of erythroo/tic stage. The protective efficacy of recombinant L. lactiswas evaluated. RESULTS： The peak parasitemias in average for the experiment groups of BALB/c and C57BL/6 mice were 0.8± 0.4% and 20.8±26.5%, respectively, and those of their control groups were 12.0±0.8% and 60.8±9.6%, respectively. None of the BALB/c mice in both experimental group and control group died during the experiment. However, all the C57BL/6 mice in the control group died within 23 d and all the vaccinated mice survived well. CONCLUSION： The results imply the potential of recombinant L. lactis as oral delivery vaccination against malaria.
基金supported by the National Natural Science Foundation of China(81271863,81361120405)the Key Research Program of the Chinese Academy of Sciences(KJZD-EW-L01)
文摘Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mecha- nism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting the understanding of pathogenesis of many bacterial, fungal and protozoan pathogens and therefore the development of novel drugs and vaccines. In the most severe malaria parasite, Plasrnodiurn falciparum, there is a major virulence gene family termed vat, by which the variant antigen PfEMP1 is encoded and expressed on the surface of parasite-infected erythrocytes. Each parasite carries about 60 anti- genically various vat genes, however, only one of which is expressed at a given time during infection. P. falciparum expresses PfEMP1s in this clonally variant manner to bind to different human endothelial re- ceptors, allowing the infected erythrocytes to sequester in tissues to escape the host＇s immune response in- cluding spleen killing and humoral immunity. At present, the mechanism of mutually exclusive expression of the var gene family remains largely unknown, even though there is increasing evidence suggesting im- portant roles of the epigenetic regulation involved in vat gene expression. In addition, epigenetic factors were also found in association with transcriptional regulation of other antigenic variant gene families in P. falciparum. In this paper, we review the current understanding of epigenetic regulations of P. falcipa- rum virulence genes with particular views toward the design of novel vaccines, drugs, and diagnosis to ma- laria.
