Poster Presentation 14th Australian Peptide Conference 2022

Formulation of mannosylated peptide-based liposomal vaccine delivery system to treat group A streptococci infection (#226)

Ummey Jannatun Nahar 1 , Jingwen Wang 1 , MD TANJIR ISLAM 1 , nedaa alharbi 1 , Prashamsa Koirala 1 , Waleed Hussein 1 , Mariusz Skwarczynski 1 , Istvan Toth 1 2 3
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
  2. School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia
  3. Institute of Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

The C-type lectin receptors (CLRs) are abundantly expressed in antigen presenting cells (APCs). APCs are the immune cells which process and present antigen to the T lymphocytes [1]. CLRs can bind with the ligands bearing terminal sugar such as mannose and thus improve antigen uptake by APCs. Peptide-based subunit vaccines are safer than the whole pathogen-based vaccines but are less immunogenic because they contain only the fragment of pathogen. Lectin receptor targeting delivery of antigen can improve the immunogenicity of peptide-based subunit vaccine [2, 3]. Liposomes are lipid based spherical carrier systems that have adjuvating effect and high encapsulation and loading capabilities [4]. Group a streptococcus (GAS) is a gram-positive bacterium responsible for more than 500, 000 deaths annually. GAS infection causes mild (pharyngitis) to severe diseases (necrotising fasciitis). The post-infection autoimmune disorder triggered by GAS infection for example rheumatic heart disease results the significant death [4]. There is no vaccine available for GAS. In this study mannosylated peptide-based liposomal vaccine is formulated to treat GAS infection.

Peptide based antigen and mannosylated ligands were synthesized by microwave assisted Fmoc and Boc-SPPS (solid phase peptide synthesis) method. All compounds were purified and characterized using HPLC and mass spectrometry. Both antigen and targeting ligands were anchored to the liposome and liposomes were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Liposomes were injected subcutaneously (tail) to the C57BL/6 mice.

All liposomes composed of antigen and targeting ligands (purity >95%, yield 10-40%) were less than 150 nm. All mannosylated liposomes produced significant IgG titres compared to negative control gr and non-mannosylated liposome group upon subcutaneous injection.

Further study is required with modification of formulation using the most effective mannose ligand of this study. The most potential mannose ligand can be used also for other vaccine formulation.

  1. Castro, S. A., & Dorfmueller, H. C. (2021). A brief review on Group A Streptococcus pathogenesis and vaccine development. Royal Society open science, 8(3), 201991.
  2. Polando, R. E., Jones, B. C., Ricardo, C., Whitcomb, J., Ballhorn, W., & McDowell, M. A. (2018). Mannose receptor (MR) and Toll‐like receptor 2 (TLR2) influence phagosome maturation during Leishmania infection. Parasite immunology, 40(4), e12521.
  3. Skwarczynski, M., & Toth, I. (2016). Peptide-based synthetic vaccines. Chemical science, 7(2), 842-854.
  4. Chatzikleanthous, D., O’Hagan, D. T., & Adamo, R. (2021). Lipid-Based Nanoparticles for Delivery of Vaccine Adjuvants and Antigens: Toward Multicomponent Vaccines. Molecular Pharmaceutics.