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 |
