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Immunogenicity of single versus mixed allele vaccines of Plasmodium vivax Duffy binding protein region II

机译：间日疟原虫达菲结合蛋白区域II的单一与混合等位基因疫苗的免疫原性

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The Duffy binding protein (DBP) of Plasmodium vivax is vital for host erythrocyte invasion. DBP region II (DBPII) contains critical residues for receptor recognition and anti-DBPII antibodies have been shown to inhibit erythrocyte binding and invasion, thereby making the molecule an attractive vaccine candidate against P. vivax blood stages. Similar to other blood-stage antigens, allelic variation within the DBPII and associated strain-specific immunity is a major challenge for development of a broadly effective vaccine against P. vivax malaria. We hypothesized that immunization with a vaccine composed of multiple DBP alleles or a modified epitope DBP (DEKnull) will be more effective in producing a broadly reactive and inhibitory antibody response to diverse DBPII alleles than a single allele vaccine. In this study, we compared single, naturally occurring DBPII allele immunizations (Sal1, 7.18, P) and DEKnull with a combination of (Sal1, 7.18, P) alleles. Quantitative analysis by ELISA demonstrated that the multiple allele vaccine tend to be more immunogenic than any of the single allele vaccines when tested for reactivity against a panel of DBPII allelic variants whereas DEKnull was less immunogenic than the mixed-allele vaccine but similar in reactivity to the single allele vaccines. Further analysis for functional efficacy by in vitro erythrocyte-binding inhibition assays demonstrated that the multiple allele immunization produced a stronger strain-neutralizing response than the other vaccination strategies even though inhibition remained biased toward some alleles. Overall, there was no correlation between antibody titer and functional inhibition. These data suggest that a multiple allele vaccine may enhance immunogenicity of a DBPII vaccine but further investigation is required to optimize this vaccine strategy to achieve broader coverage against global P. vivax strains. (C) 2013 Elsevier Ltd. All rights reserved.
机译：间日疟原虫的达菲结合蛋白（DBP）对于宿主红细胞入侵至关重要。 DBP II区（DBPII）包含用于受体识别的关键残基，并且已显示抗DBPII抗体抑制红细胞结合和入侵，从而使该分子成为对抗间日疟原虫血液阶段的有吸引力的候选疫苗。与其他血液阶段抗原类似，DBPII中的等位基因变异以及相关的菌株特异性免疫是开发抗间日疟原虫的广泛有效疫苗的主要挑战。我们假设使用由多个DBP等位基因或修饰的表位DBP（DEKnull）组成的疫苗进行免疫接种，将比单一等位基因疫苗更有效地产生对多种DBPII等位基因的广泛反应性和抑制性抗体反应。在这项研究中，我们比较了单个自然发生的DBPII等位基因免疫接种（Sal1，7.18，P）和DEKnull与（Sal1，7.18，P）等位基因的组合。 ELISA定量分析表明，在测试针对一组DBPII等位基因变体的反应性时，多等位基因疫苗倾向于比任何单等位基因疫苗更具免疫原性，而DEKnull的免疫原性低于混合等位基因疫苗，但与单等位基因疫苗。通过体外红细胞结合抑制试验对功能功效的进一步分析表明，即使抑制仍然偏向某些等位基因，多重等位基因免疫也比其他疫苗接种策略产生了更强的菌株中和反应。总体而言，抗体效价与功能抑制之间没有相关性。这些数据表明，多重等位基因疫苗可能会增强DBPII疫苗的免疫原性，但需要进一步研究以优化该疫苗策略，以实现对全球间日疟原虫菌株的更广泛覆盖。 （C）2013 Elsevier Ltd.保留所有权利。

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