Journal of Biomedical Science | |
Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis | |
Adil M Allahverdiyev1  Sezen Canim Ates1  Serap Yesilkir Baydar1  Olga N Oztel1  Serhat Elcicek2  Zeynep Akdeste1  Melahat Bagirova1  Sevil Dincer Isoglu1  Rabia Cakir Koc3  Murat Topuzogullari1  | |
[1] Department of Bioengineering, Yildiz Technical University, Istanbul, Turkey;Department of Bioengineering, Firat University, Elazig, Turkey;Department of Biomedical Engineering, Yeni Yuzyil University, Istanbul, Turkey | |
关键词: Conjugation; Leishmania; Adjuvant; Delivery; Vaccine; Polymer; | |
Others : 823853 DOI : 10.1186/1423-0127-20-35 |
|
received in 2013-02-06, accepted in 2013-05-16, 发布年份 2013 | |
【 摘 要 】
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.
【 授权许可】
2013 Topuzogullari et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140713014707435.pdf | 742KB | download | |
Figure 7. | 57KB | Image | download |
Figure 6. | 54KB | Image | download |
Figure 5. | 48KB | Image | download |
Figure 4. | 49KB | Image | download |
Figure 3. | 34KB | Image | download |
Figure 2. | 41KB | Image | download |
Figure 1. | 49KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
【 参考文献 】
- [1]Kabanov VA: From synthetic polyelectrolytes to polymer-subunit vaccines. Pure Appl Chem 2004, 76:1659-1678.
- [2]Andrianov AK, Marin A, Roberts BE: Polyphosphazene polyelectrolytes: a link between the formation of noncovalent complexes with antigenic proteins and immunostimulating activity. Biomacromolecules 2005, 6:1375-1379.
- [3]Basalp A, Mustafaeva Z, Mustafaev M: Immunogenic Cu2 + −induced biopolymer systems comprising a steroid hormone, protein antigen, and synthetic polyelectrolytes. Hybridoma 2002, 21:45-51.
- [4]Yuk SH, Cho SH, Lee HB: pH-sensitive drug delivery system using OW emulsion. J Control Release 1995, 37:69-74.
- [5]Bianchi D, Golini P, Bortolo R, Cesti P: Immobilization of penicillin G acylase on aminoalkylated polyacrylic supports. Enzyme Microb Technol 1996, 18:592-596.
- [6]Diamantstein T, Vogt W, Ruhl H, Bochert G: Stimulation of DNA synthesis in mouse lymphoid cells by polyanions in vitro. I. Target cells and possible mode of action. Eur J Immunol 1973, 3:488-493.
- [7]Kabanov VA, Mustafaev MI, Nekrasov AV, Norimov A, Petrov RV: Critical nature of the effect of the degree of polyelectrolyte polymerization on immunostimulating properties. Dokl Akad Nauk SSSR 1984, 274:998-1001.
- [8]Petrov RV, Kabanov VA, Khaitov RM, Mustafaev MI, Norimov A: Effect of heparin on the immunogenicity of electrostatic covalent albumin complexes with synthetic polyions. Immunogenicity of the triple covalent complex polyelectrolyte-protein-heparin. Mol Gen Mikrobiol Virusol 1986, 30-35.
- [9]Desjeux P: Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 2004, 27:305-318.
- [10]Pinheiro RO, Pinto EF, de Matos Guedes HL, de Mattos KA, Saraiva EM, de Mendonça SCF, Rossi-Bergmann B: Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan. Vaccine 2007, 25:2716-2722.
- [11]Hanes J, Cleland JL, Langer R: New advances in microsphere-based single-dose vaccines. Adv Drug Deliv Rev 1997, 28:97-119.
- [12]Allahverdiyev AM, Koc RC, Ates SC, Bagirova M, Elcicek S, Oztel ON: Leishmania tropica: the effect of darkness and light on biological activities in vitro. Exp Parasitol 2011, 128:318-323.
- [13]Mahoney AB, Sacks DL, Saraiva E, Modi G, Turco SJ: Intra-species and stage-specific polymorphisms in lipophosphoglycan structure control Leishmania donovani-sand fly interactions. Biochemistry 1999, 38:9813-9823.
- [14]Barron TL, Turco SJ: Quantitation of Leishmania lipophosphoglycan repeat units by capillary electrophoresis. Biochim Biophys Acta, Gen Subj 2006, 1760:710-714.
- [15]Montaudo G, Montaudo MS, Samperi F: Matrix-assisted laser desorption ionization/mass spectrometry of polymers (MALDI-MS). In Mass spectrometry of polymers. Edited by Montaudo G, Lattimer RP. Boca Raton: CRS Press LLC; 2002:431-446.
- [16]Gelfi J, Pappalardo M, Claverys C, Peralta B, Guérin JL: Safety and efficacy of an inactivated Carbopol-adjuvanted goose haemorrhagic polyomavirus vaccine for domestic geese. Avian Pathol 2010, 39:111-116.
- [17]Hilgers L, Nicolas I, Lejeune G, Dewil E, Strebelle M, Boon B: Alkyl-esters of polyacrylic acid as vaccine adjuvants. Vaccine 1998, 16:1575-1581.
- [18]Krashias G, Simon AK, Wegmann F, Kok WL, Ho LP, Stevens D, Skehel J, Heeney JL, Moghaddam AE, Sattentau QJ: Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus HA by a polyanionic carbomer. Vaccine 2010, 28:2482-2489.
- [19]Payne L, Van Nest G, Barchfeld G, Siber G, Gupta R, Jenkins S: PCPP as a parenteral adjuvant for diverse antigens. Dev Biol Stand 1998, 92:79.
- [20]Petrov R, Gvozdetskiĭ A, Gorokhov A, Evdakov V, Kabanov V: Study of the mechanisms of the action of heparin and poly-4-vinylpyridine on immunogenesis. Zh Mikrobiol Epidemiol Immunobiol 1974, 37.