Poster Presentation 11th Australian Peptide Conference 2015

Liposomes as Delivery System for Peptide-based Vaccine Against Group A Streptococcus (#101)

Khairunnisa Abdul Ghaffar , Nirmal Marasini 1 , Ashwini Giddam 1 , Michael Batzloff 2 , Michael Good 2 , Mariusz Skwarczynski 1 , Istvan Toth 1 3 4
  1. SCMB, University of Queensland, Brisbane, Queensland, Australia
  2. Institute for Glycomics, Griffifth University, Gold Coast, Queensland, Australia
  3. Pharmacy Australia Centre of Excellence, University of Queensland, Brisbane, Australia
  4. Institute of Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia

Group A Streptoccocus (GAS) is one of the top ten pathogens causing mortality and morbidity. Treatment with antibiotics has proven to be successful but a significant percentage of individuals are unresponsive once the infection turns invasive. Rheumatic heart disease is the most critical sequelae of GAS dubbed as the ‘silent killer’, claiming more than 1 million lives each year.1 Millions of healthy individuals are infected with GAS each year making the quest for a GAS vaccine of utmost importance. Our vaccine strategy utilizes the lipid core peptide (LCP) as a self-adjuvanting system2 in conjunction with liposomes as a delivery system. Liposomes are known for their efficacy in the delivery of antigens as well as for their targeting capability.3,4

The two epitopes used in this study a) J14, KQAEDKVKASREAKKQVEKALEQLEDKVK, derived from the surface associated M protein of GAS; b) P25, KLIPNASLIENCTKAEL, a universal T helper epitope. Seven different peptide antigens (unmodified and lipidated) were synthesized using standard solid phase peptide synthesis. Synthesis and purification methods were optimised to attain the final compounds with moderate to high yields (44-80%) and excellent purity (≥98%).

Following peptide synthesis, nanoliposomes were formulated via lipid dehydration-rehydration method (Figure 1). Nanoliposomes (~150 nm) had a zeta potential of +57 mV and an encapsulation efficacy of ≥65% depending on the vaccine antigen. Mice immunized intranasally with the peptides (J14 and P25) conjugated to LCP and encapsulated into liposomes elicited the highest IgG and IgA antibody titres in comparison to all vaccine candidates including positive controls which had cholera toxin B subunit. In addition, mice also retained high levels of serum IgG five months post final immunization. In conclusion, we prepared the first LCP-nanoliposome-based peptide vaccine candidate against GAS.