Synthetic is better

Gavin Painter leads a team of scientists
whose collaboration has produced exciting results in mouse trials.

Researchers from these four institutes have formed a single team, led by IRL scientists Drs Phillip Rendle and Gavin Painter, under the Foundation for Research, Science and Technology (FRST^[?]) carbohydrate nanotechnology programme.

Synthetic vaccine adjuvants, or helper compounds, designed by IRL to provoke a strong immune response when combined with other materials to make new vaccine candidates, have shown significant efficacy in tuberculosis (TB) mouse trials conducted by AgResearch. This breakthrough may also have potential applications for human cancer vaccines.

At present, the human TB vaccine known as Bacillus Calmette-Guérin (BCG) is prepared from a strain of an attenuated (weakened) live bovine TB bacillus, Mycobacterium bovis, which has lost its virulence in humans as a result of being specially cultured in an artificial medium for many years.

The protective effect of the BCG vaccine can vary significantly, and at best is 80 per cent effective in preventing TB for a limited duration. A consistently effective vaccine is desired, but regulators now require such agents to be more highly defined than in the past.

However, more defined vaccines often struggle to provoke the array of immune responses required to build effective immunity against the disease. To overcome this, vaccine adjuvants are used. Highly defined synthetic adjuvants are preferable – and this is where IRL comes in.

Dr Painter says the latest trials performed by AgReseach show IRL’s compound – a synthetic phosphoglycolipid that was designed based on structures found in the mycobacterial cell wall – helped to significantly lower the bacterial count in mice infected with TB, a result showing the team is on the right path.

“The reason this result is so exciting is that it’s very difficult to observe a statistically significant lowering of bacterial count using new synthetic vaccines based on protein antigens compared [with] live attenuated traditional vaccines like BCG.”

This is not the only milestone IRL and the extended New Zealand team of researchers have reached in this area. Further work under the same research programme with MIMR has recently shown “extremely positive” results from a synthetic adjuvant tested in a cell-based human assay.

“Specifically we have seen a huge increase in T-cell proliferation without any of the associated cellular toxicity that you might expect from such a response,” says Dr Painter.

“This is the first time we’ve seen a result of this magnitude from a single synthetic compound. We hope to use this molecule in conjunction with a new Health Research Council (HRC)-funded programme led by Dr Ian Hermans (MIMR), which will conduct human clinical cancer vaccine trials in the near future.”

The HRC programme includes the cGMP (the standard required to use the vaccine in humans) manufacture of the vaccine components at IRL’s biotechnology business unit, GlycoSyn. The addition of a New Zealand-owned adjuvant to this cancer vaccine provides a huge boost to the commercial opportunities for GlycoSyn, and Dr Painter concludes that “these are the kinds of outputs we had hoped to achieve in this multi-disciplinary research programme.”