Poster Presentation 10th Australian Peptide Conference 2013

Lipopeptide containing B-cell and T-helper epitope as intranasal vaccine candidates against Group A Streptococcus (GAS) (#132)

Saranya Chandrudu 1 , Mehfuz Zaman 1 , Mariusz Skwarczynski 1 , Michael R Batzloff 2 , Michael F Good 2 , Istvan Toth 1 3
  1. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia
  2. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
  3. Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, QLD, Australia

Group A streptococcus (GAS) infections result in a number of human diseases, including potentially life-threatening postinfectious sequelae. To protect against infection with multiple GAS serotypes, we designed and synthesized a self-adjuvanting lipopeptide (LP) 1  GAS vaccine constructs. Each lipopeptide was composed of GAS B-cell epitopes (J14 or 88/30 or incorporating both epitopes), a universal CD4+ T-cell helper epitope (P25) and an immunostimulant lipid moiety 23. The lipopeptides were synthesized using Boc-solid phase peptide synthesis (SPPS) and were self-assembled into nanoparticles 4. The immunogenicity of the nanoparticles was tested in mice and antibody titres were analyzed using ELISA. Systemic IgG antibody response was elicited in outbred swiss mice after intranasal immunization 5. In comparison, 88/30 specific IgG response was higher in the analogue containing both 88/30 and J14 epitope (LP-88/30-J14) than LP containing only 88/30 epitope (LP-88/30). Physico-chemical characterization was carried out including dynamic light scattering (DLS), transmission electron microscopy (TEM) and circular dichorism spectroscopy (CD) studies. Studies exhibited that LP-88/30-J14 formed nanoparticles of smaller size (10 nm) than LP-88/30 (100 nm). CD spectroscopy was performed to analyze the peptide conformation. Results showed that none of the tested LPs formed a typical conformational secondary structure. The current study showed that the incorporation of multiple copies of GAS peptide epitopes into a single LP construct enhanced systemic IgG antibody response to epitopes of interest. Size of the lipopeptides and immune response is mediated by the choice of peptide epitopes. These findings could provide an optimal strategy for the development of a GAS vaccine.

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  1. Skwarczynski, M.; Zaman.; M. Toth, I. Lipo-peptides/saccharides in peptide vaccine delivery. In Handbook of the Biologically Active Peptides, the 2nd Edition, Abba Kastin (Ed.), Elsevier Inc.: Burlington, Massachusetts, 2013, pp 571-579
  2. Zaman, M.; Abdel-Aal, A.-B. M.; Fujita, Y.; Ziora, Z. M.; Batzloff, M. R.; Good, M. F.; Toth, I. Structure-activity relationship for the development of a self-adjuvanting mucosally active lipopeptide vaccine against Streptococcus pyogenes. Journal of Medicinal Chemistry 2012, 55, 8515-8523
  3. Zaman, M.; Abdel-Aal, A. B. M.; Fujita, Y.; Phillipps, K. S. M.; Batzloff, M. R.; Good, M. F.; Toth, I. Immunological evaluation of lipopeptide group A streptococcus (GAS) vaccine: structure-activity relationship. PLoS One 2012, 7, e30146
  4. Skwarczynski, M.; Toth, I. Peptide-based Subunit Nanovaccines Curr. Drug Deliv. 2011, 8, 282-289
  5. Zaman, M.; Chandrudu, S.; Toth, I. Strategies for intranasal delivery of vaccines. Drug Delivery and Translational Research 2012, 3, 100-109