Cracking the vaccine conundrum

As GP surgeries switch to high flu alert, vaccine expert and pharmacology lecturer Anne Moore tells Catherine Shanahan that chicken eggs are key to developing the annual flu vaccine

So it all goes back to the chicken and the egg, or, to be more precise, chicken eggs.

The old tried-and-tested method of producing an annual flu vaccine involves injecting millions of embryonated eggs. This is the most common method of producing a flu vaccine and it’s been on the go for decades.

Before getting to the eggs though, the World Health Organisation (WHO) and its flu experts hold a scientific meeting in February every year where the physical make-up of the vaccine to counter the following winter’s flu in the northern hemisphere is determined. This is based on an informed analysis of the strains circulating in the population and how immunogenic (capable of inducing an immune response) they are. “They make a prediction as to what strains are most likely to be circulating come flu season,” says Dr Moore. “They then formulate what they consider to be the appropriate vaccine response.”

Dr Moore says there are three components in the vaccine developed for the 2014/2015 seasonal influenza campaign: They are the proteins (termed antigens) from the 2009 H1N1 virus, (popularly known as ‘swine flu)’; H3N2 and a B-like virus. These were identified as the viruses most likely to be circulating come the winter months. The problem with this “best guess” approach is that viruses, by their nature, mutate, and by the time flu season arrives, the vaccine developed may not be an optimal match. That appears to be the case this year — the H3N2 virus underwent what Dr Moore describes as “antigenic drift”, in other words it mutated, not by much, but enough to make the vaccine less effective. How effective or ineffective it is will not be fully understood until the end of the flu season, Dr Moore says.

But back to the eggs. After its February summit, the WHO produces its vaccine wishlist — the ingredients or “proteins” it considers necessary to produce the optimal vaccine. These ingredients are used to grow up a vaccine variant in a lab. Dr Moore says two proteins from each of the three viruses are used: the HA (‘H’) and NA antigens. “They put that variant on the backbone of a safe virus and inject eggs to allow the virus to grow. They suck out the content of the eggs and kill everything off and break up the virus so that it is dead. They then purify out the H and N proteins and those are then formulated into a vaccine.”

The eggs used are fertilised hen eggs and are incubated for a number of days to allow the virus replicate before harvesting the virus-containing fluid. Contrary to popular belief, the flu shot administered in Ireland does not contain any live viruses because they are killed off in the production process.

The process of producing an annual flu vaccine takes months, hence the need to get cracking as early as February. “Growing up sufficient doses of a vaccine does take a long time, you have to give enough time to produce a high-quality product for use in the general population. It’s not something that can be done in a week. As soon as the WHO releases the strains, work starts, and it takes until the following September,” says Dr Moore.

The sudden arrival of swine flu back in 2009 gave no such window for producing a vaccine. In this case there was “shift” rather than “drift” in the virus involved.

“It was a completely new virus, it was swine, avian and human, all rolled into one,” says Dr Moore. The main concern was the shift would cause a pandemic and that there would be no immunity in the population.

“It turns out there was. The human body saw something in that virus that was a little similar to something it had seen before.”

This is the key to an effective vaccine — producing something the immune system will recognise. If it does, the body knows what to do to fight infection. If it doesn’t have any memory of the virus — due to mutation — it takes longer to generate a response, during which time the virus, if fit enough, will continue to grow in the host.

The constantly changing nature of viruses means an annual flu jab is essential, tailored to whatever viruses are considered most likely to be dominant that year. Dr Moore says the Holy Grail for scientists involved in this area of research is a universal flu jab. As Dr Moore points out, this would involve a vaccine that enabled the immune system to not only recognise existing viruses, but also viruses that will exist in the future. While she is working with Oxford University to develop a vaccine that recognises as broad a range of viruses as possible, thus broadening the immune response, she concedes that a universal jab “realistically, is highly unlikely to be achieved”. Instead, booster immunisations with a universal vaccine, maybe every five to 10 years, may be possible.

Dr Moore is also working on a less painful way of delivering the vaccine instead of the current needle-stick approach. Her technology, the ImmuPatch, is essentially a patch fitted with dissolvable microneedles made from a vaccine-containing formulation that are simply pressed against the skin to release the vaccine. Not only is it less painful, it makes sense economically she says, because unlike liquid vaccines, it doesn’t require cold storage, making it much cheaper to store, ship and deliver, and it has a much longer shelf-life. However, she has yet to secure a backer to get her patch to clinical trial.

In the meantime, it’s down to the doctor’s surgery for the annual jab in the knowledge that some vaccine is better than none. Dr Moore says protection against three influenza viruses is possible.

“Just because the virus circulating is a little different to what was predicted doesn’t mean it’s ineffective. It does keep the level of infection down, it reduces morbidity and mortality. If you are at risk of influenza infection, you should ensure that you get vaccinated.”

Dr Moore is a lecturer in pharmacology at UCC’s school of pharmacy