Abstract

BackgroundThe 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.ResultsWe 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.ConclusionsOur 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.

Highlights

  • 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

  • Induction of an effective immune response has been reported in human cells stimulated with phosphodiester bond CpG-DNA (PO-ODN) and non-CpG dinucleotides flanked by specific base sequences (CpG-DNA) encapsulated in cationic liposomes such as N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) and lipofectin [20,21]

  • Effects of CpG-DNA encapsulated in liposomes on IL-8 promoter activation To identify the conditions driving the effective immunomodulatory activity of PO-ODN in humans, we encapsulated MB-ODN 4531(O) in several different liposomes and compared the abilities of the complexes to stimulate immune responses in human and mouse cells

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Summary

Introduction

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 formulated adjuvants such as flagella and CpG-DNA to enhance the magnitude of immune responses. Several studies have suggested that PSODN induces backbone-related side effects, such as transient splenomegaly [15], lymphoid follicle destruction [16], arthritis [17], and PS-ODN-specific IgM production [18] in PS-ODN-treated mice. Induction of an effective immune response has been reported in human cells stimulated with PO-ODN and non-CpG-DNA encapsulated in cationic liposomes such as N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) and lipofectin [20,21]

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