Department of Microbiology, College of Medicine, Hallym University, Gangwon-do 200-702, Republic of Korea.
BMC Immunol. 2011 May 18;12:29. doi: 10.1186/1471-2172-12-29.
The screening of peptide-based epitopes has been studied extensively for the purpose of developing therapeutic antibodies and prophylactic vaccines that can be potentially useful for treating cancer and infectious diseases such as influenza virus, malaria, hepatitis B, and HIV. To improve the efficacy of antibody production by epitope-based immunization, researchers evaluated liposomes as a means of delivering vaccines; they also formulated adjuvants such as flagella and CpG-DNA to enhance the magnitude of immune responses. Here, we provide a potent method for peptide-based epitope screening and antibody production without conventional carriers.
We present that a particular form of natural phosphodiester bond CpG-DNA encapsulated in a specific liposome complex (Lipoplex(O)) induces potent immunomodulatory activity in humans as well as in mice. Additionally, Lipoplex(O) enhances the production of IgG2a specific to antigenic protein in mice. Most importantly, immunization of mice with several peptides co-encapsulated with Lipoplex(O) without carriers significantly induces each peptide-specific IgG2a production in a TLR9-dependent manner. A peptide-specific monoclonal antibody produced against hepatocellular carcinoma-associated antigen has functional effects on the cancer cells.
Our overall results show that Lipoplex(O) is a potent adjuvant and that complexes of peptide and Lipoplex(O) are extremely useful for B cell epitope screening and antibody production without carriers. Therefore, our strategy may be promptly used for the development of therapeutic antibodies by rapid screening of potent B cell epitopes.
为了开发治疗癌症和流感病毒、疟疾、乙肝、艾滋病毒等传染病的治疗性抗体和预防性疫苗,人们广泛研究了基于肽的表位筛选。为了提高基于表位免疫的抗体产生效率,研究人员评估了脂质体作为疫苗传递的一种手段;他们还设计了鞭毛和 CpG-DNA 等佐剂来增强免疫反应的强度。在这里,我们提供了一种无需传统载体即可进行基于肽的表位筛选和抗体生产的有效方法。
我们提出一种特殊形式的天然磷酸二酯键 CpG-DNA 包裹在特定的脂质体复合物(Lipoplex(O))中,可在人类和小鼠中诱导有效的免疫调节活性。此外,Lipoplex(O)增强了针对抗原蛋白的 IgG2a 的产生。最重要的是,用几种与 Lipoplex(O)共包封的肽免疫小鼠,在 TLR9 依赖性方式下,可显著诱导每种肽特异性 IgG2a 的产生。针对肝癌相关抗原产生的肽特异性单克隆抗体对癌细胞具有功能作用。
我们的总体结果表明,Lipoplex(O)是一种有效的佐剂,并且肽和 Lipoplex(O)的复合物在没有载体的情况下对于 B 细胞表位筛选和抗体生产非常有用。因此,我们的策略可以通过快速筛选有效的 B 细胞表位,迅速用于治疗性抗体的开发。