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首页> 外文期刊>Infection and immunity >Comparison of Immunogenicities of Recombinant Plasmodium vivax Merozoite Surface Protein 1 19- and 42-Kilodalton Fragments Expressed in Escherichia coli
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Comparison of Immunogenicities of Recombinant Plasmodium vivax Merozoite Surface Protein 1 19- and 42-Kilodalton Fragments Expressed in Escherichia coli

机译：重组间日疟原虫裂殖子表面蛋白1 19和42 Kilodalton片段在大肠杆菌中表达的免疫原性的比较。

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The 42- and 19-kDa C-terminal fragments of merozoite surface protein 1 (MSP-142 and MSP-119, respectively) are both promising blood-stage vaccine candidate antigens. At present, it is not clear which of the two antigens will be more suitable for inclusion in a cocktail malaria vaccine. In the present study, we expressed the two C-terminal fragments of Plasmodium vivax MSP-1 (PvMSP-1) in an Escherichia coli expression system and purified them by using a rapid two-step protocol. Both of the products were recognized by monoclonal antibodies against PvMSP-1 as well as by immune sera from several individuals exposed to P. vivax. We analyzed and compared the immunological responses to recombinant PvMSP-119 and PvMSP-142 in mice by using six different adjuvant formulations. Moderate to high antibody responses were observed with both of the antigens in different adjuvant formulations. Surprisingly, alum, which is generally considered to be a poor adjuvant for recombinant malaria antigens, was found to be as good an adjuvant as Montanide ISA 720, ASO2A, and other adjuvant formulations. Most adjuvant formulations induced high levels of immunoglobulin G1 (IgG1), followed by IgG3 and IgG2. Lymphocytes from animals in the PvMSP-142- and PvMSP-119-immunized groups showed proliferative responses upon stimulation with the respective antigens, and high levels of interleukin-4 (IL-4), IL-5, and gamma interferon were detected in the culture supernatants. Immunodepletion studies with sera from mice immunized with these two antigens showed that while immunization with PvMSP-142 does produce a PvMSP-119-specific response, a substantial portion is also focused on structures in PvMSP-142 not represented by the epidermal growth factor-like domains of PvMSP-119. These findings may have implications for the design of MSP-1-based vaccine constructs.
机译：裂殖子表面蛋白1的42和19 kDa C端片段（分别为MSP-1 42 和MSP-1 19 ）都是有前途的血液疫苗候选抗原。目前，尚不清楚两种抗原中的哪一种更适合包含在鸡尾酒型疟疾疫苗中。在本研究中，我们在大肠杆菌表达系统中表达了间日疟原虫MSP-1（PvMSP-1）的两个C端片段，并使用快速的两步协议。两种产品均被抗PvMSP-1的单克隆抗体以及暴露于 P的几个个体的免疫血清所识别。 vivax 。我们通过使用六种不同的佐剂制剂，分析并比较了对重组PvMSP-1 19 和PvMSP-1 42 的免疫反应。在不同的佐剂制剂中，两种抗原均观察到中等至高抗体应答。令人惊讶地，发现通常被认为是重组疟疾抗原的不良佐剂的明矾与Montanide ISA 720，ASO2A和其他佐剂制剂一样好。大多数佐剂制剂诱导高水平的免疫球蛋白G1（IgG1），其次是IgG3和IgG2。 PvMSP-1 42 -和PvMSP-1 19 免疫组的动物淋巴细胞在受到相应抗原刺激后表现出增殖反应，并且白细胞介素4（在培养上清液中检测到IL-4），IL-5和γ干扰素。用这两种抗原免疫的小鼠的血清贫血研究表明，虽然用PvMSP-1 42 免疫确实会产生PvMSP-1 19 特异性反应，但很大一部分也是重点研究了PvMSP-1 19 的表皮生长因子样结构域所不代表的PvMSP-1 42 中的结构。这些发现可能对基于MSP-1的疫苗构建体的设计有影响。

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