Acquah Festus K, Obboh Evans K, Asare Kwame, Boampong Johnson N, Nuvor Samuel Victor, Singh Susheel K, Theisen Michael, Williamson Kim C, Amoah Linda Eva
Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana.
Malar J. 2017 Aug 1;16(1):306. doi: 10.1186/s12936-017-1955-0.
Recent advances in malaria control efforts have led to an increased number of national malaria control programmes implementing pre-elimination measures and demonstrated the need to develop new tools to track and control malaria transmission. Key to understanding transmission is monitoring the prevalence and immune response against the sexual stages of the parasite, known as gametocytes, which are responsible for transmission. Sexual-stage specific antigens, Pfs230 and Pfs48/45, have been identified and shown to be targets for transmission blocking antibodies, but they have been difficult to produce recombinantly in the absence of a fusion partner.
Regions of Pfs48/45 and Pfs230 known to contain transmission blocking epitopes, 6C and C0, respectively, were produced in a Lactococcus lactis expression system and used in enzyme linked immunosorbent assays to determine the seroreactivity of 95 malaria patients living in the Central Region of Ghana.
Pfs48/45.6C and Pfs230.C0 were successfully produced in L. lactis in the absence of a fusion partner using a simplified purification scheme. Seroprevalence for L. lactis-produced Pfs48/45.6C and Pfs230.C0 in the study population was 74.7 and 72.8%, respectively.
A significant age-dependent increase in antibody titers was observed, which suggests a vaccine targeting these antigens could be boosted during a natural infection in the field.
疟疾控制工作的最新进展使得越来越多的国家疟疾控制项目实施消除前措施,并表明需要开发新工具来追踪和控制疟疾传播。了解传播的关键在于监测针对寄生虫有性阶段(即配子体,负责传播)的流行率和免疫反应。已鉴定出性阶段特异性抗原Pfs230和Pfs48/45,并表明它们是传播阻断抗体的靶点,但在没有融合伴侣的情况下,很难通过重组方式生产。
分别在乳酸乳球菌表达系统中生产已知含有传播阻断表位的Pfs48/45和Pfs230区域(分别为6C和C0),并用于酶联免疫吸附测定,以确定95名生活在加纳中部地区的疟疾患者的血清反应性。
使用简化的纯化方案,在没有融合伴侣的情况下,Pfs48/45.6C和Pfs230.C0在乳酸乳球菌中成功生产。研究人群中乳酸乳球菌生产的Pfs48/45.6C和Pfs230.C0的血清阳性率分别为74.7%和72.8%。
观察到抗体滴度有显著的年龄依赖性增加,这表明针对这些抗原的疫苗在野外自然感染期间可能会得到加强。