Poster Presentation 8th Australasian Vaccines & Immunotherapeutics Development Meeting 2020

Development of C-type Lectin Receptor Targeting Subunit Vaccine Against Group a Streptococcus (GAS) (#312)

Ummey Jannatun Nahar 1 , MD TANJIR ISLAM 1 , nedaa alharbi 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 for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

Introduction: Antigen presenting cells (APCs) are the immune cells which process and present antigen to the T lymphocytes to mediate the immune response1. Most common APCs are dendritic cell (DC) and macrophage which contain affluent C-type lectin receptors (CLRs) on their surfaces. The CLRs are the transmembrane receptors possessing the ability of binding of the sugar such as mannose containing ligands2. Since subunit vaccines contain only the fragment of small antigen, these are instinctively less immunogenic3. To overcome the poor immunogenicity, CLRs are the popular targets of subunit vaccines. Because if the carbohydrate moiety such as mannose is used in vaccine construct, it favours the uptake of antigen and consequently the following steps for improved immune response4. GAS infection costs over 639,000 deaths annually mostly due to post-infection autoimmune disorder rhematic heart disease (RHD)5,6. Over the decades research couldn’t result yet any GAS vaccine to resolve the GAS infection burden. Therefore, this study aimed to the development of CLR targeting subunit vaccine against GAS.

Experimental: Synthesis of peptide antigen and mannosylated ligands have been accomplished via Boc-SPPS (solid phase peptide synthesis). Peptides were purified by preparative HPLC and characterized by analytical HPLC and ESI-MS. Both antigen and mannose targeting ligands have been anchored to the liposome delivery system to prepare nano vaccine. All formulations were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM).

Result: Peptide antigen and mannosylated targeting ligands were synthesized and purified (purity>95%). Peptide anchored liposome formulations were extruded to get the nanoparticle vaccine (<150nm, PDI <0.1).

Conclusion: Antigen and receptor targeting ligands have been successfully synthesized and used to prepare liposomal nanoparticle. In-vivo study is required to find out the most effective targeting ligand for antigen uptake by APCs.

References:

  1. Zhang, C., Wang, G. & Zhu, B. Application of antigen presenting cell-targeted nanovaccine delivery system in rhabdovirus disease prophylactics using fish as a model organism. J Nanobiotechnol18, 24 (2020).
  2. Polando, R. E., et al. (2018). Mannose receptor (MR) and Toll-like receptor 2 (TLR2) influence phagosome maturation during Leishmania infection. Parasite Immunol 40(4): e12521.
  3. Skwarczynski, M. and I. Toth (2016). Peptide-based synthetic vaccines. Chem Sci 7(2): 842-854.
  4. Chen, P., et al. (2016). Dendritic cell targeted vaccines: Recent progresses and challenges. Hum Vaccin Immunother 12(3): 612-622.
  5. Hand, R. M., Snelling, T. L., Carapetis, J. R. Group A Streptococcus. InHunter's Tropical Medicine and Emerging Infectious Diseases 2020 Jan 1 (pp. 429-438). Content Repository Only!.
  6. Azuar, A., Jin, W., Mukaida, S., Hussein, W.M., Toth, I. and Skwarczynski, M., 2019. Recent advances in the development of peptide vaccines and their delivery systems against group A streptococcus. Vaccines, 7(3):58.