Scanning microscopy solves vaccine problem

With 85% of the world’s farmed deer being in New Zealand, susceptibility to yersiniosis, a disease associated with stress in young deer, is a serious concern in the multi-million dollar deer industry.

The bacterium is widespread in the environment and if a fawn’s immune response is affected by stress the bacterium can invade the intestine. The lining can be damaged so badly the fawn cannot absorb water and food, can develop serious bloody diarrhoea, dehydrate and die.

Although the disease is treatable with antibiotics, fawns can wander far afield and, if not treated in time, will die.

Fortunately, AgResearch scientists developed Yersiniavax, the only vaccine in the world specifically for deer, in the 1980’s. It is now distributed to NZ
veterinarians by Upper-Hutt based Intervet New Zealand, which has now merged with Schering Plough Animal Health, making the combined entity the world’s biggest animal health company.

Intervet discovered in 2006 that a small number of veterinarians were experiencing difficulties dispensing the vaccine through the draw-off tube attached to the vaccinating gun. Air was entering the vaccination barrel and something was impeding the non-return valve in the instrument.

Initially, it was believed the problem was with the vaccination gun itself, but several other models were trialled and still the problem persisted. Investigations then began into the design of the Vaxipack, the soft plastic vaccine container, but without success.

It was only when Intervet began studying the vaccine itself under a microscope that ‘rogue’ crystals were discovered in the product, so samples were sent for study at Industrial Research’s Scanning Electron Microscopy (SEM) facility, says Intervet’s Technical and R & D Manager, Robert Dempster.

“By 2pm the next day we had received a report back which not only gave us a photograph of the crystals but also gave us the dimensions and what the crystals were made of,” he says.

IRL’s scanning electron microscopy facility examines surfaces, capturing images and providing magnification of from 20,000 to 50,000 times the original. With its companion EDX (Energy Dispersive X-Ray) ability, elemental analysis of samples as small as one square micron can also be provided.

By looking at the magnesium-to-phosphate ratio in the SEM analysis results, IRL GlycoSyn chemical engineer, Graham Caygill then determined that newberyite, a highly insoluble species of magnesium phosphate, was causing the problem. Intervet was subsequently able to reformulate the vaccine to avoid the problem recurring.

“This was really a multi-disciplinary issue and a good example of classic fault analysis,” says Graham.

“Working both within IRL and together with our client, we were able to firstly identify the crystals, determine why the fault happened, and come up with a solution to the problem.”

“It’s difficult to put a figure on just how much being able to solve this problem has saved us but, suffice to say, it has been a significant amount,” says Robert Dempster.

“Not only that, being able to go back to veterinarians now and tell them we know what caused the problem and that we have put in place a solution has been invaluable.”