Hviid Lars
Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
Hum Vaccin. 2010 Jan;6(1):84-9. doi: 10.4161/hv.6.1.9602. Epub 2010 Jan 23.
There is substantial immuno-epidemiological evidence that the parasite-encoded, so-called variant surface antigens (VSAs), such as PfEMP1 on the surface of infected erythrocytes (IEs) are important-in some cases probably decisive determinants of clinical outcome of P. falciparum malaria. The evidence is increasingly being underpinned by specific molecular understanding of the pathogenic processes involved. Pregnancy-associated malaria (PAM) caused by placenta-sequestering IEs expressing the PfEMP1 variant VAR2CSA is a particularly striking example of this. These findings have raised hopes that development of PfEMP1-based vaccines to protect specifically against severe malaria syndromes-in particular PAM-is feasible. This review summarizes the evidence that VSAs are important targets of NAI, discusses why VSA-based vaccines might be feasible despite the extensive intra- and interclonal variation of VSAs, and how vaccines based on this type of antigens fit into the current global strategy to reduce, eliminate and eventually eradicate the burden of malaria.
有大量免疫流行病学证据表明，寄生虫编码的所谓变异表面抗原（VSA），如感染红细胞（IE）表面的恶性疟原虫红细胞膜蛋白1（PfEMP1），在某些情况下可能是恶性疟原虫疟疾临床结局的重要——甚至可能是决定性——决定因素。越来越多的证据得到了对所涉及致病过程的具体分子理解的支持。由表达PfEMP1变体VAR2CSA的胎盘滞留IE引起的妊娠相关疟疾（PAM）就是一个特别突出的例子。这些发现让人们燃起了希望，即开发基于PfEMP1的疫苗以特异性预防严重疟疾综合征——尤其是PAM——是可行的。本综述总结了VSA是天然获得性免疫（NAI）重要靶点的证据，讨论了尽管VSA存在广泛的克隆内和克隆间变异，但基于VSA的疫苗为何可能可行，以及基于此类抗原的疫苗如何融入当前减少、消除并最终根除疟疾负担的全球战略。
