Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Lipid Peptide Core Nanoparticles as Multivalent Vaccine Candidates against Streptococcus pyogenes

Mariusz Skwarczynski A , Bibi Hamideh Parhiz A , Fatemeh Soltani A , Saranya Srinivasan A , Khairul A. Kamaruzaman A , I-Chun Lin A and Istvan Toth A B
+ Author Affiliations
- Author Affiliations

A The University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, Qld 4072, Australia.

B Corresponding author. Email: i.toth@uq.edu.au

Australian Journal of Chemistry 65(1) 35-39 https://doi.org/10.1071/CH11292
Submitted: 15 July 2011  Accepted: 9 September 2011   Published: 3 October 2011

Abstract

Traditional vaccine approaches for Group A streptococcus (GAS) infection are inadequate owing to the host’s production of cross-reactive antibodies that recognize not only the bacteria but also human tissue. To overcome this problem a peptide subunit-based vaccine was proposed, which would incorporate only minimal non-cross reactive epitopes. However, special delivery systems/adjuvants were required because short peptides are not immunogenic. In this study we have incorporated two epitopes from two different GAS proteins into a lipid core peptide (LCP) self-adjuvanting delivery system to achieve better protection against a wide range of GAS serotypes. Multivalent and monovalent constructs were synthesized with the help of an azide alkyne cycloaddition (click) reaction and their ability to self-assemble under aqueous conditions was examined. The compounds significantly differed in their ability to form small size nanoparticles, which are believed to be most appropriate for peptide-based subunit vaccine delivery. The LCP conjugates possessing two different epitopes, in contrast to monoepitopic constructs, formed small nanoparticles (5–15 nm) presumably owing to a suitable hydrophilic-hydrophobic balance of the molecules.


References

[1]  M. R. Batzloff, K. S. Sriprakash, M. F. Good, Curr. Drug Targets 2004, 5, 57.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXjvVKisA%3D%3D&md5=48e871bc36c59a55b209e3dbbe343e40CAS |

[2]  J. R. Carapetis, A. C. Steer, E. K. Mulholland, M. Weber, Lancet Infect. Dis. 2005, 5, 685.
         | Crossref | GoogleScholarGoogle Scholar |

[3]  M. F. Good, H. J. Xu, M. Batzloff, Int. J. Parasitol. 2002, 32, 575.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xis1eisb4%3D&md5=8f436e83bc858fb080c101ea0a606de5CAS |

[4]  A. Severin, E. Nickbarg, J. Wooters, S. A. Quazi, Y. V. Matsuka, E. Murphy, I. K. Moutsatsos, R. J. Zagursky, S. B. Olmsted, J. Bacteriol. 2007, 189, 1514.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXitl2isb0%3D&md5=41d10b3c473b0a9076ebab4643b58de0CAS |

[5]  V. A. Fischetti, Clin. Microbiol. Rev. 1989, 2, 285.
         | 1:STN:280:DyaL1MzlsVaisw%3D%3D&md5=b9ada0bd56a2f616ca5524d02cdc6c8aCAS |

[6]  S. Pruksakorn, B. Currie, E. Brandt, D. Martin, A. Galbraith, C. Phornphutkul, S. Hunsakunachai, A. Manmontri, M. F. Good, Lancet 1994, 344, 639.
         | Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2czlt1WjsQ%3D%3D&md5=1ce905e9571efd0b14eb2285ae5e5de3CAS |

[7]  S. Pruksakorn, B. Currie, E. Brandt, C. Phornphutkul, S. Hunsakunachai, A. Manmontri, J. H. Robinson, M. A. Kehoe, A. Galbraith, M. F. Good, Int. Immunol. 1994, 6, 1235.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXhslyksbo%3D&md5=c390cc18eb76078510426333cd626e52CAS |

[8]  W. A. Hayman, E. R. Brandt, W. A. Relf, J. Cooper, A. Saul, M. F. Good, Int. Immunol. 1997, 9, 1723.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXns1Kis78%3D&md5=51d43951cd71a3cb20f00185bf3bb83eCAS |

[9]  C. A. Guzman, S. R. Talay, G. Molinari, E. Medina, G. S. Chhatwal, J. Infect. Dis. 1999, 179, 901.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXitlSls7o%3D&md5=eee3603052e01c8fa3edf738f07c9e22CAS |

[10]  K. Schulze, C. Olive, T. Ebensen, C. A. Guzman, Vaccine 2006, 24, 6088.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XotV2ntb8%3D&md5=056b3e75bfe2619898929ca7753a0c3eCAS |

[11]  W. Zhong, M. Skwarczynski, I. Toth, Aust. J. Chem. 2009, 62, 956.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFensbzM&md5=15b97c0683b2384479e49f8a47ccb700CAS |

[12]  I. Toth, P. Simerska, Y. Fujita, Int. J. Pept. Res. Ther. 2008, 14, 333.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsVKjt7vM&md5=070e8c6b1f47b7bdfeee647d173413b6CAS |

[13]  M. Zaman, A. M. Abdel-Aal, K. S. M. Phillipps, Y. Fujita, M. F. Good, I. Toth, Vaccine 2010, 28, 2243.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXisFOmurw%3D&md5=60f0f7b41609be3a3c98ca6a715542f1CAS |

[14]  K. S. M. Phillipps, M. N. Wykes, X. Q. Liu, M. Brown, J. Blanchfield, I. Toth, Immunology 2009, 128, e582.
         | Crossref | GoogleScholarGoogle Scholar |

[15]  W. Zhong, M. Skwarczynski, Y. Fujita, P. Simerska, M. F. Good, I. Toth, Aust. J. Chem. 2009, 62, 993.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFensb3K&md5=4a37ba571a64ea731d83277f4d60038cCAS |

[16]  W. Zhong, M. Skwarczynski, P. Simerska, M. F. Good, I. Toth, Tetrahedron 2009, 65, 3459.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjsl2ht7c%3D&md5=f9127c30751c924c32b4b77296ffdbfdCAS |

[17]  M. Zaman, M. Skwarczynski, J. M. Malcolm, C. N. Urbani, Z. F. Jia, M. R. Batzloff, M. F. Good, M. J. Monteiro, I. Toth, Nanomed.-Nanotechnol. 2011, 7, 168.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXltFGjsL8%3D&md5=f2c09c670774992c71f19d78e8bd59efCAS |

[18]  M. Skwarczynski, M. Zaman, C. N. Urbani, I. C. Lin, Z. F. Jia, M. R. Batzloff, M. F. Good, M. F. Monteiro, I. Toth, Angew. Chem. Int. Ed. 2010, 49, 5742.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXps1Cqsbo%3D&md5=100dd8a207e812dd10227f38115c56c5CAS |

[19]  A. B. M. Abdel-Aal, M. Zaman, Y. Fujita, M. R. Batzloff, M. F. Good, I. Toth, J. Med. Chem. 2010, 53, 8041.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlGntrzN&md5=791ec319f81b91ca40bbab380ffedffbCAS |

[20]  W. Zhong, M. Skwarczynski, I. Toth, Curr. Drug Deliv. 2009, 6, 520.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXntlam&md5=bdb45aa33343d41a934d008bce5e399dCAS |

[21]  M. S. Shaila, R. Nayak, S. S. Prakash, M. Georgousakis, E. Brandt, D. J. McMillan, M. R. Batzloff, S. Pruksakorn, M. F. Good, K. S. Sriprakash, Vaccine 2007, 25, 3567.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksV2qsLk%3D&md5=09e8cb10cc32d686116b6140a0295341CAS |

[22]  M. Skwarczynski, A. A. H. Ahmad Fuaad, L. Rustanti, Z. M. Ziora, M. Aqil, M. R. Batzloff, M. F. Good, I. Toth, Drug Deliv. Lett. 2011, 1, 2.

[23]  C. Olive, K. Schulze, H. K. Sun, T. Ebensen, A. Horvath, I. Toth, C. A. Guzman, Vaccine 2007, 25, 1789.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlarsLo%3D&md5=f235e74df68561b3edc5210810de4ffaCAS |

[24]  M. Meldal, C. W. Tornoe, Chem. Rev. 2008, 108, 2952.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXps1yhurk%3D&md5=f39fbe60a8f73dd67d3770168745ba84CAS |

[25]  M. Skwarczynski, I. Toth, Curr. Drug Deliv. 2011, 8, 282.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXls1Ojs7Y%3D&md5=15965692c62e197ba89ff4fcf53a8ae0CAS |

[26]  C. N. Urbani, C. A. Bell, M. R. Whittaker, M. J. Monteiro, Macromolecules 2008, 41, 1057.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtFylsLY%3D&md5=64b81fb7cf3e3648bef61637d04358e7CAS |

[27]  S. D. Xiang, A. Scholzen, G. Minigo, C. David, V. Apostolopoulos, P. L. Mottram, M. Plebanski, Methods 2006, 40, 1.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XpvFGiu7k%3D&md5=568287212584840850b8569dc4e1b516CAS |

[28]  M. Skwarczynski, Z. M. Ziora, D. J. Coles, I. C. Lin, I. Toth, Chem. Commun. (Camb.) 2010, 46, 3140.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlt1Cku7o%3D&md5=d9f947e3885c07200f1757edd3eb672bCAS |

[29]  Z. M. Ziora, N. Wimmer, R. New, M. Skwarczynski, I. Toth, Carbohydr. Res. 2011, 346, 1439.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXosFSqs7o%3D&md5=a93c5e13522d3c4a5e2120194cf5b52bCAS |

[30]  A. S. Abdelrahim, Z. M. Ziora, J. A. Bergeon, A. R. Moss, I. Toth, Tetrahedron 2009, 65, 9436.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXht1Gnu7jL&md5=4b01ca369a29ee154dbfdb926f15e1abCAS |

[31]  A. B. M. Abdel-Aal, M. R. Batzloff, Y. Fujita, N. Barozzi, A. Faria, P. Simerska, P. M. Moyle, M. F. Good, I. Toth, J. Med. Chem. 2008, 51, 167.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVWgurzL&md5=caa4394f67fe77d831165902360e0de0CAS |