Abstract
Disadvantages of classical vaccines, such as the risk of an autoimmune reaction, might be overcome by using a subunit vaccine containing the minimal microbial components necessary to stimulate appropriate immune responses. However, vaccines based on minimal epitopes suffer from poor immunogenicity and require the use of an additional immunostimulant (adjuvant). Only a few adjuvants have been permitted for use with vaccines intended for human administration. We have developed several vaccine candidates based on a lipid-core-peptide (LCP) system. This system has self-adjuvanting properties, and it can be used for the delivery of a variety of epitopes to produce vaccine candidates against a targeted disease. The LCP system is easily assembled by simple stepwise Boc solid-phase peptide synthesis.
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References
Zhong, W., Skwarczynski, M., and Toth, I. (2009) Lipid Core Peptide System for Gene, Drug, and Vaccine Delivery, Aust. J. Chem. 62, 956–967.
Moyle, P. M., and Toth, I. (2008) Self-adjuvanting lipopeptide vaccines, Curr. Med. Chem. 15, 506–516.
Zhong, W., Skwarczynski, M., Fujita, Y., Simerska, P., Good, M. F., and Toth, I. (2009) Design and Synthesis of Lipopeptide-Carbohydrate Assembled Multivalent Vaccine Candidates Using Native Chemical Ligation, Aust. J. Chem. 62, 993–999.
Zhong, W., Skwarczynski, M., Simerska, P., Good, M. F., and Toth, I. (2009) Development of highly pure alpha-helical lipoglycopeptides as self-adjuvanting vaccines, Tetrahedron 65, 3459–3464.
Fujita, Y., Moyle, P. M., Hieu, S., Simerska, P., and Toth, I. (2008) Investigation toward multi-epitope vaccine candidates using native chemical ligation, Biopolymers 90, 624–632.
Moyle, P. M., Olive, C., Ho, M. F., Good, M. F., and Toth, I. (2006) Synthesis of a highly pure lipid core peptide based self-adjuvanting triepitopic group A Streptococcal vaccine, and subsequent immunological evaluation, J. Med. Chem. 49, 6364–6370.
Simerska, P., Abdel-Aal, A. B. M., Fujita, Y., Moyle, P. M., McGeary, R. P., Batzloff, M. R., Olive, C., Good, M. F., and Toth, I. (2008) Development of a liposaccharide-based delivery system and its application to the design of group a streptococcal vaccines, J. Med. Chem. 51, 1447–1452.
Moyle, P. M., Olive, C., Karpati, L., Barozzi, N., Ho, M. F., Dyer, J., Sun, H. K., Good, M., and Toth, I. (2005) Synthesis and immunological evaluation of M protein targeted tetra-valent and tri-valent group A streptococcal vaccine candidates based on the lipid-core peptide system, Int. J. Pept. Res. Ther. 12, 317–326.
Hayman, W. A., Toth, I., Flinn, N., Scanlon, M., and Good, M. F. (2002) Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical group A streptococcal peptide vaccine candidate from the M protein using lipid-core peptide technology, Immunol. Cell Biol. 80, 178–187.
Abdel-Aal, A. B. M., Batzloff, M. R., Fujita, Y., Barozzi, N., Faria, A., Simerska, P., Moyle, P. M., Good, M. F., and Toth, I. (2008) Structure-activity relationship of a series of synthetic lipopeptide self-adjuvanting group A streptococcal vaccine candidates, J. Med. Chem. 51, 167–172.
Olive, C., Hsien, K., Horvath, A., Clair, T., Yarwood, P., Toth, I., and Good, M. F. (2004) Protection against group A streptococcal infection by vaccination with self-adjuvanting lipid core M protein peptides, Vaccine 23, 2298–2303.
Olive, C., Batzloff, M. R., Horvath, A., Wong, A., Clair, T., Yarwood, P., Toth, I., and Good, M. F. (2002) A lipid core peptide construct containing a conserved region determinant of the group a streptococcal M protein elicits heterologous opsonic antibodies, Infect. Immun. 70, 2734–2738.
Horvath, A., Olive, C., Wong, A., Clair, T., Yarwood, P., Good, M., and Toth, I. (2002) A lipophilic adjuvant carrier system for antigenic peptides, Lett. Pept. Sci. 8, 285–288.
Cemazar, M., and Craik, D. J. (2008) Microwave-assisted Boc-solid phase peptide synthesis of cyclic cysteine-rich peptides,J. Pept. Sci. 14, 683–689.
Gibbons, W. A., Hughes, R. A., Charalambous, M., Christodoulou, M., Szeto, A., Aulabaugh, A. E., Mascagni, P., and Toth, I. (1990) Lipidic peptides.1. Synthesis, resolution and structural elucidation of lipidic amino-acids and their homo-oligomers and heterooligomers, Liebigs Ann. Chem., 1175–1183.
Schnolzer, M., Alewood, P., Jones, A., Alewood, D., and Kent, S. B. H. (2007) In situ neutralization in boc-chemistry solid phase peptide synthesis - Rapid, high yield assembly of difficult sequences, Int. J. Pept. Res. Ther. 13, 31–44.
Schnolzer, M., Alewood, P., Jones, A., Alewood, D., and Kent, S. B. H. (1992) In situ neutralization in boc-chemistry solid phase peptide synthesis - Rapid, high yield assembly of difficult sequences, Int. J. Pept. Protein Res. 40, 180–193.
Sarin, V. K., Kent, S. B. H., Tam, J. P., and Merrifield, R. B. (1981) Quantitative monitoring of solid phase peptide-synthesis by the ninhydrin reaction Anal. Biochem. 117, 147–157.
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This work was supported by the National Health and Medicinal Research Council (Australia).
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Skwarczynski, M., Toth, I. (2011). Lipid-Core-Peptide System for Self-Adjuvanting Synthetic Vaccine Delivery. In: Mark, S. (eds) Bioconjugation Protocols. Methods in Molecular Biology, vol 751. Humana Press. https://doi.org/10.1007/978-1-61779-151-2_18
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DOI: https://doi.org/10.1007/978-1-61779-151-2_18
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