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疫苗佐剂 CpG(寡脱氧核苷酸 ODNs)、MPL(3-O-去酰化单磷酰脂质 A)和纳洛酮增强了对小鼠疟原虫重组血小板反应蛋白相关黏附蛋白(TRAP)的 Th1 免疫应答。

Vaccine adjuvants CpG (oligodeoxynucleotides ODNs), MPL (3-O-deacylated monophosphoryl lipid A) and naloxone-enhanced Th1 immune response to the Plasmodium vivax recombinant thrombospondin-related adhesive protein (TRAP) in mice.

机构信息

Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Pasteur Avenue, Tehran, P.O. Box 1316943551, Iran.

Sorbonne Universités, UPMC Univ Paris 06, Inserm (Institut National de la Santé et de la Recherche Medicale), Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, ERL CNRS 8255 (Centre National de la Recherche Scientifique), 91 Boulevard de l'Hôpital, 75013, Paris, France.

出版信息

Med Microbiol Immunol. 2018 Nov;207(5-6):271-286. doi: 10.1007/s00430-018-0545-2. Epub 2018 Jun 9.

DOI:10.1007/s00430-018-0545-2
PMID:29948091
Abstract

Despite considerable efforts toward vaccine development over decades, there is no available effective vaccine against Plasmodium vivax. Thrombospondin-related adhesive protein of P. vivax (PvTRAP) is essential for sporozoite motility and invasions into mosquito's salivary gland and vertebrate's hepatocyte; hence, it is a promising target for pre-erythrocytic vaccine. In the current investigation, the role of antibodies and cellular immune responses induced by purified recombinant PvTRAP (rPvTRAP) delivered in three adjuvants, naloxone (NLX), CpG oligodeoxynucleotides ODN1826 (CpG-ODN), and 3-O-deacylated monophosphoryl lipid A (MPL), alone and in combination was evaluated in immunized C57BL/6 mice. The highest level and the avidity of anti-PvTRAP IgG (mean OD 2.55), IgG2b (mean OD 1.68), and IgG2c (mean OD 1.466) were identified in the group received rPvTRA/NLX-MPL-CpG. This group also presented the highest IgG2c/IgG1 (2.58) and IgG2b/IgG1 (2.95) ratio when compared to all other groups, and among the adjuvant groups, the lowest IgG2c/IgG1 (1.86) and IgG2b/IgG1 (2.25) ratio was observed in mice receiving rPvTRAP/NLX. Mice receiving rPvTRAP/adjuvants induced significantly the higher levels of interferon gamma (IFN-γ), low level of detectable IL-10, and no detectable IL-4 production. The present result revealed that PvTRAP is immunogenic and its administration with CPG, MPL, and NLX in C57BL/6 mice induced Th1 immune response. Besides, the rPvTRAP delivery in the mixed formulation of those adjuvants had more potential to increase the level, avidity, and persistence of anti-TRAP antibodies. However, it warrants further assessment to test the blocking activity of the produced antibodies in immunized mice with different adjuvant formulations.

摘要

尽管几十年来在疫苗开发方面做出了巨大努力,但目前仍没有针对间日疟原虫的有效疫苗。间日疟原虫血影蛋白相关黏附蛋白(PvTRAP)对于子孢子的运动以及入侵蚊子唾液腺和脊椎动物肝细胞是必需的;因此,它是一种有前途的原虫疫苗靶点。在本研究中,评估了在三种佐剂(纳洛酮(NLX)、CpG 寡脱氧核苷酸 ODN1826(CpG-ODN)和 3-O-脱酰基单磷酰脂质 A(MPL))中单独和组合递呈的纯化重组 PvTRAP(rPvTRAP)诱导的抗体和细胞免疫应答在免疫 C57BL/6 小鼠中的作用。在接受 rPvTRA/NLX-MPL-CpG 的组中,观察到抗 PvTRAP IgG(平均 OD2.55)、IgG2b(平均 OD1.68)和 IgG2c(平均 OD1.466)的水平和亲和力最高。与所有其他组相比,该组还表现出最高的 IgG2c/IgG1(2.58)和 IgG2b/IgG1(2.95)比值,而在佐剂组中,接受 rPvTRAP/NLX 的小鼠的 IgG2c/IgG1(1.86)和 IgG2b/IgG1(2.25)比值最低。接受 rPvTRAP/佐剂的小鼠诱导了显著更高水平的干扰素 γ(IFN-γ)、低水平可检测的白细胞介素 10(IL-10)和未检测到白细胞介素 4(IL-4)的产生。本研究结果表明 PvTRAP 具有免疫原性,其在 C57BL/6 小鼠中与 CPG、MPL 和 NLX 联合使用可诱导 Th1 免疫反应。此外,在这些佐剂的混合配方中递送 rPvTRAP 具有增加抗 TRAP 抗体的水平、亲和力和持久性的更大潜力。然而,需要进一步评估不同佐剂配方免疫小鼠产生的抗体的阻断活性。

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