Mapping Epitopes of the Plasmodium vivax Duffy Binding Protein with Naturally Acquired Inhibitory Antibodies
Mapping Epitopes of the Plasmodium vivax Duffy Binding Protein with Naturally Acquired Inhibitory Antibodies
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DOI：
10.1128/iai.01036-09
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发表时间：
2010-03-01
影响因子：
3.1
通讯作者：
Adams, John H.
中科院分区：
文献类型：
--
作者：
Chootong, Patchanee;Ntumngia, Francis B.;Adams, John H.
间日疟原虫达菲结合蛋白（DBP）是一种对血期感染至关重要的卵裂子微基配体，这使其成为针对间日疟疾的抗体介导免疫的重要候选疫苗。用线性肽阵列的差异筛选比较了非抑制性和抑制性高滴度人免疫血清的反应性，以确定与保护性免疫相关的目标表位。在巴布亚新几内亚间日疟高度流行地区的居民中观察到的自然获得性抗dbp特异性血清学反应显示，随着时间的推移，dbp特异性滴度发生了显著变化。每种血清的抗DBP功能抑制范围从完全抑制到无抑制，即使对DBP高滴度应答者也是如此，这表明表位特异性很重要。抑制性免疫人抗体在DBP （SalI）配体结构域上鉴定出与抑制反应显著相关的特异性b细胞线性表位。这些表位上亲和纯化的天然获得抗体可显著抑制DBP红细胞结合功能，证实了特异性表位的保护价值。这些结果代表了我们对间日疟原虫的部分血期免疫和疫苗诱导抗体保护的一些特定靶点的理解的重要进展。
Plasmodium vivax Duffy binding protein (DBP) is a merozoite microneme ligand vital for blood-stage infection, which makes it an important candidate vaccine for antibody-mediated immunity against vivax malaria. A differential screen with a linear peptide array compared the reactivities of noninhibitory and inhibitory high-titer human immune sera to identify target epitopes associated with protective immunity. Naturally acquired anti-DBP-specific serologic responses observed in the residents of a region of Papua New Guinea where P. vivax is highly endemic exhibited significant changes in DBP-specific titers over time. The anti-DBP functional inhibition for each serum ranged from complete inhibition to no inhibition even for high-titer responders to the DBP, indicating that epitope specificity is important. Inhibitory immune human antibodies identified specific B-cell linear epitopes on the DBP (SalI) ligand domain that showed significant correlations with inhibitory responses. Affinity-purified naturally acquired antibodies on these epitopes inhibited the DBP erythrocyte binding function greatly, confirming the protective value of specific epitopes. These results represent an important advance in our understanding of part of blood-stage immunity to P. vivax and some of the specific targets for vaccine-elicited antibody protection.