Influence of HLA-DRB1 Alleles on Antibody Responses to PfCP-2.9-Immunized and Naturally Infected Individuals
Influence of HLA-DRB1 Alleles on Antibody Responses to PfCP-2.9-Immunized and Naturally Infected Individuals
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HLA-DRB1 等位基因对 PfCP-2.9 免疫和自然感染个体抗体反应的影响
DOI：
10.1007/s10875-009-9281-0
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发表时间：
2009
影响因子：
9.1
通讯作者：
Weiqing Pan
中科院分区：
文献类型：
--
作者：
Qingfeng Zhang;Xiangyang Xue;Xin;Cuiping Wang;Wenjun Chang;Weiqing Pan
恶性疟原虫嵌合蛋白PfCP-2.9是由顶端膜抗原（AMA）-1（III）和裂殖子表面蛋白（MSP）1-19组成的嵌合蛋白，是一种很有前途的无性期疟疾疫苗，目前正在进行临床试验。本研究旨在探讨人类白细胞抗原（HLA）-DRB 1基因型与PfCP-2.9抗体应答之间的潜在关联。材料与方法采用等位基因序列特异性引物聚合酶链反应（PCR）技术，对40名I期试验参与者和86名中国南方疟疾患者的HLA-DRB 1等位基因进行了检测。酶联免疫吸附试验和T淋巴细胞增殖试验测定了PfCP-2.9或其组分的抗体和细胞反应。结果在临床受试者中，抗PfCP-2.9抗体反应可能被HLA-DR 6等位基因抑制，这与T淋巴细胞增殖试验一致。然而，HLA-DR 7与自然感染个体的抗体应答呈正相关，而DR 8与所有三种重组蛋白的较弱抗体应答相关。此外，寄生虫血症是显着较低的样品具有较高的抗体水平对PfCP-2.9或rMSP 1 -19，但不是拉马-1（III）。ConclusionThese data suggest，抗体反应对PfCP-2.9，AMA-1（III），或MSP 1 -19引起的疫苗制剂或自然感染是由不同的HLA-II等位基因控制。此外，对MSP 1 -19的抗体应答比AMA-1（III）对保护性免疫的贡献更大。
IntroductionThe Plasmodium falciparum chimeric protein, PfCP-2.9, which consists of apical membrane antigen (AMA)-1(III) and merozoite surface protein (MSP)1–19, is a promising asexual-stage malaria vaccine currently being evaluated in clinical trials. This study attempts to investigate the potential association between human leukocyte antigen (HLA)-DRB1 genotype and antibody response against PfCP-2.9 in healthy population and malaria patients.Materials and methodsWe investigated the HLA-DRB1 alleles in 40 participants from phase I trial and 86 malaria patients from southern China by polymerase chain reaction with allele sequence-specific primers. The antibody and cellular response against PfCP-2.9 or its components were measured by enzyme-linked immunosorbent assay and T lymphocyte proliferation assay.ResultsIn clinical subjects, the anti-PfCP-2.9 antibody response was likely suppressed by HLA-DR6 alleles, which was consistent with the T lymphocyte proliferation assay. Nevertheless, HLA-DR7 positively correlated with antibody responses in naturally infected individuals while DR8 correlated with weaker antibody responses for all the three recombinant proteins. Moreover, parasitemia was significantly lower in samples with higher antibody levels against PfCP-2.9 or rMSP1–19, but not for rAMA-1(III).ConclusionThese data suggest that antibody responses against PfCP-2.9, AMA-1(III), or MSP1–19 elicited by vaccine formulation or natural infection are controlled by different HLA-II alleles. Moreover, the antibody response to MSP1–19 contributed more to protection immunity than AMA-1(III).
DOI：
10.1073/pnas.0501594102
发表时间：
2005-04-12
影响因子：
11.1
作者：
Kato, K;Mayer, DCG;Miller, LH
通讯作者：
Miller, LH