Novel TLR2 agonist adjuvant vaccine

By exploring the properties of complex compounds, researchers from the University are discovering new kinds of vaccines to combat disease in Indonesia. This technology can help vaccinate against hepatitis, diphtheria and tetanus.

The technology

S-[2,3-bis(palmitoyloxy)propyl] cysteine, (Pam2Cys) – which corresponds to the lipid component of macrophage activating lipopeptide 2 (MALP-2) from Mycoplasma fermentans – is a potent immuno-adjuvant when conjugated to the antigen. Its mode of action appears to rely on the ability of Pam2Cys to interact with Toll-like receptor 2 (TLR2) on dendritic cells (DC), which triggers DC maturation and results in an increased efficiency of presentation of the peptide epitopes.

Although candidate TLR adjuvants are effective at promoting vaccine efficacy, it is known in the field that superior immune responses (especially T cell responses) are generated when both TLR ligand and antigens are (covalently) linked.

University of Melbourne researchers, led by Professor David Jackson, from the Department of Microbiology and Immunology (Faculty of Medicine, Dentistry and Health Sciences), have engineered Pam2Cys to incorporate a unique branched structure capable of complexing (through electrostatic interactions) charged polypeptides/proteins.

Two lead products have been generated:

  • one with N-terminal arginine residues which is positively charged
  • one with N-terminal glutamic acid residues which is negatively charged

Binding of a charged branched lipopeptide to oppositely charged protein/peptide antigen (Ag) results in the formation of stable complexes and occurs at physiologic pH and salt concentrations.

In vivo POC data have been generated in a number of models, including H1N1 influenza split virus, TB (ESAT-6 recombinant protein) and HCV VLP, showing strong B and T cell responses.

The partnership

Bio Farma is the one and only vaccine and antisera producer for humans in Indonesia. Currently, the needs for EPI vaccines in Indonesia have been supplied solely by Bio Farma by manufacturing and distributing more than 1.7 billion doses of vaccine per year to meet the needs of EPI vaccine for the national immunisation program.

Bio Farma has an outstanding international reputation based on the WHO prequalification for all of its Expanded Program on Immunisation vaccines (EPI) vaccine products. At this moment, Bio Farma products are exported to countries around the world through the direct distribution or through various agencies such as UNICEF. Bio Farma has obtained the Best Export Performance from the Trade Ministry of Indonesia in 2010, 2011 and 2012 as the proof for its consistent exceptional performance.

The outcome

In December 2012, The University of Melbourne announced an option and evaluation agreement with PT Bio Farma to develop this TLR2 agonist-based adjuvant which could boost the effectiveness of vaccines for a range of infectious diseases including Hepatitis C, Diphtheria, Tetanus, Pertussis, Hepatitis B and Haemopilus influenza type B.

Under the proposed arrangement, the University of Melbourne will receive research funding to further evaluate this technology.

The research agreement was facilitated by UoM Commercial Ltd, the University's Commercial Engagement Service company.

Additional information can be found on the University of Melbourne newsroom.