Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
Nat Commun. 2011 Dec 20;2:601. doi: 10.1038/ncomms1615.
Current vaccine strategies against the asexual blood stage of Plasmodium falciparum are mostly focused on well-studied merozoite antigens that induce immune responses after natural exposure, but have yet to induce robust protection in any clinical trial. Here we compare human-compatible viral-vectored vaccines targeting ten different blood-stage antigens. We show that the full-length P. falciparum reticulocyte-binding protein homologue 5 (PfRH5) is highly susceptible to cross-strain neutralizing vaccine-induced antibodies, out-performing all other antigens delivered by the same vaccine platform. We find that, despite being susceptible to antibody, PfRH5 is unlikely to be under substantial immune selection pressure; there is minimal acquisition of anti-PfRH5 IgG antibodies in malaria-exposed Kenyans. These data challenge the widespread beliefs that any merozoite antigen that is highly susceptible to immune attack would be subject to significant levels of antigenic polymorphism, and that erythrocyte invasion by P. falciparum is a degenerate process involving a series of parallel redundant pathways.
目前针对恶性疟原虫无性血期的疫苗策略主要集中在研究充分的裂殖子抗原上，这些抗原在自然感染后能诱导免疫反应，但在任何临床试验中都未能诱导出强大的保护作用。在这里，我们比较了针对十种不同血期抗原的与人相容的病毒载体疫苗。我们表明，全长恶性疟原虫网织红细胞结合蛋白同源物 5（PfRH5）极易受到交叉株中和疫苗诱导的抗体的攻击，优于同一疫苗平台所提供的所有其他抗原。我们发现，尽管 PfRH5 容易受到抗体的攻击，但它不太可能受到实质性的免疫选择压力；在疟疾流行的肯尼亚人中，很少有抗 PfRH5 IgG 抗体的获得。这些数据挑战了广泛存在的观点，即任何极易受到免疫攻击的裂殖子抗原都将受到显著的抗原多态性的影响，而且恶性疟原虫对红细胞的入侵是一个退化的过程，涉及一系列平行的冗余途径。
