Neutralizing antibodies induced by liposomal HIV-1 glycoprotein 41 peptide simultaneously bind to both the 2F5 or 4E10 epitope and lipid epitopes
Neutralizing antibodies induced by liposomal HIV-1 glycoprotein 41 peptide simultaneously bind to both the 2F5 or 4E10 epitope and lipid epitopes
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DOI：
10.1097/qad.0b013e32832faea5
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发表时间：
2009-10-23
期刊：
影响因子：
3.8
通讯作者：
Alving, Carl R.
中科院分区：
文献类型：
--
作者：
Matyas, Gary R.;Wieczorek, Lindsay;Alving, Carl R.
目标：需要开发 HIV-1 疫苗制剂，其中包含廉价的抗原和临床可接受的有效佐剂，用于诱导中和抗体。这项初始疫苗研究的目的是生产肽和脂质诱导的鼠单克隆抗体，其复制 2175 和/或 4E10 人类抗体的特征，结合糖蛋白 41 的近膜外部区域 (MPER) 和相邻的脂质双层，以中和 CD4(+) 淋巴细胞的 HIV-1 感染。 研究设计 和方法：使用含有合成MPER肽作为肽抗原、磷脂酰肌醇-4-磷酸(PIP)作为脂质抗原、单磷酰脂质A作为有效佐剂的脂质体作为制剂来免疫小鼠。然后生产 mAb，并测试其与 MPER、糖蛋白 41 和 PIP 的结合，以及在人外周血单核细胞测定中中和 CD4+ 细胞的 HIV-1 感染的能力。 结果：多克隆抗血清含有与 MPER 和 PIP 结合的抗体。产生的免疫球蛋白 M mAb 既与 2175 的核心 MPER 位点结合，又与 4E10 位点重叠，同时与 PIP 结合。高浓度的这些 mAb 中和了 HIV-1 初级感染性分子克隆对外周血淋巴细胞的感染。结论：含有 MPER 肽作为抗原、PIP 作为脂质抗原、脂质 A 作为佐剂的脂质体诱导抗 MPER 特异性多特异性抗体，这些抗体同时结合糖蛋白 41 MPER 和邻近的脂质并在人外周血单核细胞测定中中和 HIV-1 感染。 (C) 2009 年威科健康 |利平科特·威廉姆斯·威尔金斯
Objectives: There is a need to develop HIV-1 vaccine formulations that incorporate inexpensive antigens and clinically acceptable potent adjuvants for inducing neutralizing antibodies. The purpose of this initial vaccine study was to produce peptide- and lipid-induced murine mAbs that replicate the characteristics of the 2175 and/or 4E10 human antibodies in binding both to the membrane proximal external region (MPER) of glycoprotein 41 and the adjacent lipid bilayer for neutralizing HIV-1 infection of CD4(+) lymphocytes.Research designs and methods: Liposomes containing a synthetic MPER peptide as a peptide antigen, phosphatidylinositol-4-phosphate (PIP) as a lipid antigen, and monophosphoryl lipid A as a potent adjuvant were used as a formulation to immunize mice. mAbs were then produced and tested for binding to MPER, glycoprotein 41, and PIP and for the ability to neutralize HIV-1 infection of CD4+ cells in a human peripheral blood mononuclear cell assay.Results: Polyclonal antisera contained antibodies that bound both to MPER and PIP. Immunoglobulin M mAbs were produced that bound both to the core MPER site of 2175, or that overlapped with the 4E10 site, and that simultaneously bound PIP. High concentrations of these mAbs neutralized infection of peripheral blood lymphocytes by a primary infectious molecular clone of HIV-1.Conclusion: Liposomes containing MPER peptide as an antigen, PIP as a lipid antigen, and lipid A as an adjuvant induce anti-MPER-specific multispecific antibodies that simultaneously bind glycoprotein 41 MPER and adjacent lipid and neutralize HIV-1 infection in a human peripheral blood mononuclear cell assay. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins