Abstract
Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.
Highlights
The research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character compared to classical adjuvants [1,2]
Gel Permeation Chromatography (GPC) chromatograms of LPG-polyacrylic acid (PAA) conjugates prepared with 10 and 5 mM NaIO4 and individual PAA are shown in Figure 2, where PAA concentrations were equal in all solutions
The chemical structure of LPG was modified to obtain amine groups for conjugation, but this change in structure can alter antigenicity so that modification was kept minimal by lowering the oxidation agent (NaIO4) concentration
Summary
The research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character compared to classical adjuvants [1,2]. The mechanism behind the immunogenic activity of polyelectrolyte-antigen conjugates, proposed by Kabanov [1], is based on the interaction of the conjugate with membrane proteins of immune-competent cells. Free polyelectrolyte chains of the conjugate clusters the membrane proteins and antigen linked with polyelectrolyte is presented to the receptor on the cell membrane. In this study researchers reported that low molecular weight synthetic polyelectrolytes did not show any activity in in vivo tests, implying that the effect becomes pronounced with increased molecular weight [7,8]
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