当前位置: X-MOL 学术npj Vaccines › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Outer membrane protein complex as a carrier for malaria transmission blocking antigen Pfs230
npj Vaccines ( IF 9.2 ) Pub Date : 2019-07-08 , DOI: 10.1038/s41541-019-0121-9
Puthupparampil V. Scaria , Christopher G. Rowe , Beth B. Chen , Olga V. Muratova , Elizabeth R. Fischer , Emma K. Barnafo , Charles F. Anderson , Irfan U. Zaidi , Lynn E. Lambert , Bob J. Lucas , Debbie D. Nahas , David L. Narum , Patrick E. Duffy

Malaria transmission blocking vaccines (TBV) target the mosquito stage of parasite development by passive immunization of mosquitoes feeding on a vaccinated human. Through uptake of vaccine-induced antibodies in a blood meal, mosquito infection is halted and hence transmission to another human host is blocked. Pfs230 is a gametocyte and gamete surface antigen currently under clinical evaluation as a TBV candidate. We have previously shown that chemical conjugation of poorly immunogenic TBV antigens to Exoprotein A (EPA) can enhance their immunogenicity. Here, we assessed Outer Membrane Protein Complex (OMPC), a membrane vesicle derived from Neisseria meningitidis, as a carrier for Pfs230. We prepared Pfs230-OMPC conjugates with varying levels of antigen load and examined immunogenicity in mice. Chemical conjugation of Pfs230 to OMPC enhanced immunogenicity and functional activity of the Pfs230 antigen, and OMPC conjugates achieved 2-fold to 20-fold higher antibody titers than Pfs230-EPA/AdjuPhos® at different doses. OMPC conjugates were highly immunogenic even at low doses, indicating a dose-sparing effect. EPA conjugates induced an IgG subclass profile biased towards a Th2 response, whereas OMPC conjugates induced a strong Th1-biased immune response with high levels of IgG2, which can benefit Pfs230 antibody functional activity, which depends on complement activation. OMPC is a promising carrier for Pfs230 vaccines.



中文翻译:

外膜蛋白复合物作为疟疾传播阻断抗原Pfs230的载体

疟疾传播阻断疫苗(TBV)通过被动免疫以接种疫苗的人类为食的蚊子来靶向寄生虫发展的蚊子阶段。通过在血粉中摄取疫苗诱导的抗体,蚊子感染得以中止,从而阻止了向其他人宿主的传播。Pfs230是一种配子细胞和配子表面抗原,目前正作为TBV候选药物进行临床评估。先前我们已经表明,免疫原性较差的TBV抗原与外蛋白A(EPA)的化学缀合可以增强其免疫原性。在这里,我们评估了外膜蛋白复合物(OMPC),一种源自脑膜炎奈瑟氏球菌的膜囊泡,作为Pfs230的载体。我们准备了具有不同抗原负载水平的Pfs230-OMPC共轭物,并检查了小鼠的免疫原性。Pfs230的到OMPC化学缀合增强的免疫原性和抗原Pfs230的功能活性,和OMPC缀合物实现2倍至20倍高的抗体滴度比Pfs230-EPA / AdjuPhos ®以不同的剂量。OMPC偶联物即使在低剂量下也具有很高的免疫原性,这表明它具有节省剂量的作用。EPA偶联物诱导偏向Th2应答的IgG亚类分布,而OMPC偶联物诱导高水平IgG2的强烈Th1偏向的免疫应答,这可以有益于Pfs230抗体的功能活性,这取决于补体激活。OMPC是Pfs230疫苗的有希望的载体。

更新日期:2019-11-18
down
wechat
bug