Plasmodium vivax recombinant vaccine candidate AMA-1 plays an important role in adaptive immune response eliciting differentiation of dendritic cells

Plasmodium vivax recombinant vaccine candidate AMA-1 plays an important role in adaptive immune response eliciting differentiation of dendritic cells
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DOI:
10.1016/j.vaccine.2009.07.031
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发表时间:
2009-09-18
期刊:
影响因子:
5.5
通讯作者:
Braga, Erika Martins
Braga, Erika Martins
中科院分区:
医学3区
文献类型:
--
作者:
Bueno, Lilian Lacerda;Morais, Cristiane Guimaraes;Braga, Erika Martins

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顶膜抗原-1 (Apical Membrane antigen -1, AMA-1)是一种特征明确且功能重要的merozoite蛋白,目前被认为是疟疾疫苗的主要候选抗原。先前,我们发现AMA-1对疟疾初发受试者的细胞免疫反应有影响,导致单核细胞来源的树突状细胞的替代激活,并通过受刺激的pbmc诱导促炎反应。虽然人类和动物疟疾模型系统有证据表明,细胞介导的免疫可能有助于保护和发病机制,但对间日疟疾的细胞免疫反应和可能调节这种免疫的因素了解甚少。在目前的工作中,我们描述了间日疟原虫自然感染个体的单核细胞来源树突状细胞的成熟,以及间日疟原虫候选疫苗Pv-AMA-1对相同供者免疫反应的影响。我们发现疟疾感染的受试者存在DC成熟的调节,表现为抗原呈递分子(CD1a, HLA-ABC和HLA-DR),辅助分子(CD40, CD80和CD86)和Fc γ RI (CD64)受体(P
The Apical Membrane Antigen-1 (AMA-1) is a well-characterized and functionally important merozoite protein and is currently considered a major candidate antigen for a malaria vaccine. Previously, we showed that AMA-1 has an influence on cellular immune responses of malaria-naive subjects, resulting in an alternative activation of monocyte-derived dendritic cells and induction of a pro-inflammatory response by stimulated PBMCs. Although there is evidence, from human and animal malaria model systems that cell-mediated immunity may contribute to both protection and pathogenesis, the knowledge on cellular immune responses in vivax malaria and the factors that may regulate this immunity are poorly understood. In the current work, we describe the maturation of monocyte-derived dendritic cells of P. vivax naturally infected individuals and the effect of P. vivax vaccine candidate Pv-AMA-1 on the immune responses of the same donors. We show that malaria-infected subjects present modulation of DC maturation, demonstrated by a significant decrease in expression of antigen-presenting molecules (CD1a, HLA-ABC and HLA-DR), accessory molecules (CD40, CD80 and CD86) and Fc gamma RI (CD64) receptor (P