Bongfen Silayuv E, Ntsama Patricia M, Offner Sandra, Smith Thomas, Felger Ingrid, Tanner Marcel, Alonso Pedro, Nebie Issa, Romero Jackeline F, Silvie Olivier, Torgler Ralph, Corradin Giampietro
Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Vaccine. 2009 Jan 7;27(2):328-35. doi: 10.1016/j.vaccine.2008.09.097. Epub 2008 Nov 5.
The N-terminal domain of the circumsporozoite protein (CSP) has been largely neglected in the search for a malaria vaccine in spite of being a target of inhibitory antibodies and protective T cell responses in mice. Thus, in order to develop this region as a vaccine candidate to be eventually associated with other candidates and, in particular, with the very advanced C-terminal counterpart, synthetic constructs representing N- and C-terminal regions of Plasmodium falciparum and Plasmodium berghei CSP were administered as single or combined formulations in mice. We show that the antisera generated against the combinations inhibit sporozoite invasion of hepatocytes in vitro better than antisera against single peptides. Furthermore, two different P. falciparum CSP N-terminal constructs (PfCS22-110 and PfCS65-110) were recognized by serum samples from people living in malaria-endemic regions. Importantly, recognition of the short N-terminal peptide (PfCS65-110) by sera from children living in a malaria-endemic region was associated with protection from disease. Taken together, these results underline the potential of using such fragments as malaria vaccine candidates.
尽管环子孢子蛋白（CSP）的N端结构域是小鼠体内抑制性抗体和保护性T细胞反应的靶点，但在寻找疟疾疫苗的过程中，该结构域在很大程度上被忽视了。因此，为了将该区域开发成一种最终可与其他候选疫苗联合使用，特别是与非常先进的C端对应物联合使用的候选疫苗，代表恶性疟原虫和伯氏疟原虫CSP的N端和C端区域的合成构建体以单一或联合制剂的形式在小鼠中给药。我们发现，针对联合制剂产生的抗血清在体外抑制子孢子侵袭肝细胞的效果优于针对单个肽段产生的抗血清。此外，来自疟疾流行地区人群的血清样本识别出了两种不同的恶性疟原虫CSP N端构建体（PfCS22-110和PfCS65-110）。重要的是，来自疟疾流行地区儿童的血清对短N端肽段（PfCS65-110）的识别与疾病预防相关。综上所述，这些结果突显了使用此类片段作为疟疾候选疫苗的潜力。
