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Hyperstable Vaccines

Technology platform for vaccine design useful for multiple indications in infectious diseases, cancer, & autoimmunity.

Proof of concept demonstrated with a potentially universal oral influenza vaccine candidate.

Background

Worldwide vaccination programs save millions of lives annually. However, temperature-sensitivity and need for delivery by injection for these sensitive biological compounds cause substantial hurdles in development and deployment. WHO estimates that up to 80% of cost of a vaccination campaign is from the cold chain & 50% of the wastage is from breaks in the cold chain.

Furthermore, some vaccines in market have significant limitations, e.g. influenza vaccines that require seasonal updates, making scale-up and stockpiling difficult.

JCU researchers have used synthetic biology to generate hyper-stable vaccines that bypass the need for cold chain transport and offer the potential for oral delivery. The technology is a platform technology based on D-amino acid combinatorial chemistry. The vast majority of proteins in nature are constructed from L-amino acids, which are highly susceptible to degradation by endogenous proteases. In contrast, D-amino acids are intrinsically resistant to degradation. We are creating synthetic antigens using D-aminoacids that achieve similar structural configurations & offer more stable alternatives (Fig. 1).

figure 1.

Fig.1: Structural modelling indicates that the native (A) and our synthetic (B) agonist form similar overall confirmations despite differing primary sequences.

We have early-stage results with influenza & EBV. The summary of results with influenza vaccine candidate are as follows: We reverse engineered a conserved CD8+ T cell agonist into fully artificial antigen. The synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus-specific CD8+ T cells more than natural antigen. Mice vaccinated with artificial antigen survived a lethal influenza challenge significantly more than a control group. Moreover, the synthetic agonist was immunogenic after oral administration & stable in varying temperature conditions (room temperature & freezing).

The benefits of the technology is to create synthetic antigens that offer stable & immunogenic alternatives to conventional vaccines.

Advantages of our influenza vaccine candidate are:

  • Hyperstable
  • Potential oral activity
  • Potential universal vaccine
  • May not require frequent changes
  • Easy to scale up/stock supplies against pandemics

This is a platform technology applicable to developing vaccines for infectious diseases & cancer, and other peptides. The pipeline includes candidates for EBV, CMV, cancer immunotherapy, etc.

We are seeking funding & support to take forward the lead candidate through preclinical development, as well as collaboration on pipeline development.

Publications

J Clin Invest. 2018;128(4):1569-1580. https://doi.org/10.1172/JCI91512

Patent

WO2018064718: Peptide Libraries and methods of use (Filed from QIMR)