The cell line or the egg?
Predicting exactly what flu strains will circulate each year to create the seasonal flu vaccine is an imperfect science and one that sometimes fails. Now the results of a decade-long study looking at a new way of growing influenza viruses could be the answer to creating more effective vaccines.
Influenza vaccines are used each year to combat seasonal and potential pandemic influenza viruses.
As influenza viruses mutate and evolve continuously in nature, influenza vaccines must be updated each year. As some strains mutate more rapidly than others, the vaccines that are developed are not always a perfect match for the virus which is circulating.
A team of scientists at the Doherty Institute, led by Royal Melbourne Hospital Ms Heidi Peck, Head of Serology at the WHO Collaborating Centre for Reference and Research on Influenza at the Doherty Institute, has shown that growing influenza viruses in specialised cell lines, rather than chicken eggs, improves the likelihood they will match circulating influenza viruses.
They are hopeful that the findings which they published in npj Vaccines, could lead to more effective flu vaccines.
Ms Peck explains that most flu vaccines are still made using the traditional method where Candidate Vaccine Viruses (or CVVs) are grown in chicken eggs, before being inactivated and formulated into the seasonal or pandemic vaccines.
Chicken eggs have been the preferred medium since the 1950s, as the eggs allow the virus to grow to a high level. However, while preferred, the medium is far from perfect.
“Some seasonal influenza viruses cannot be adapted to grow in eggs,” explains Peck.
“There was a situation a few years ago where the circulating strain of H3N2 just wouldn’t grow in the eggs. So, we were left in a situation where we couldn’t put one of the primary circulating strains into the vaccine.
“If we aren’t able to shop from the entire list of viruses, the potential of leaving out circulating strains is obviously greater and the vaccine is not going to be as effective.”
Using specialised cell lines instead of eggs to grow the virus, could mitigate this risk.
Senior author on the paper Royal Melbourne Hospital Professor Ian Barr, Deputy Director of the WHO Collaborating Centre for Reference and Research on Influenza explains that this is because the influenza virus isolation rates in the cells, meaning the likelihood that the virus will grow, is at least twice as good as those in eggs.
“If we put five viruses into an egg, we might see two grow. However, when put them into cell lines, its likely all five will grow,” explains Professor Barr.
There’s also the added benefit that cell lines are a more stable medium. “When we grow CVVs in eggs, the viral surface protein, known as the haemagglutinin protein, often changes,” says Professor Barr.
This is because influenza presents very differently in birds - as an infection in the gut rather than the respiratory system. Therefore, it must adapt in order to grow.
These mutations have an impact and may reduce the effectiveness of some components of the vaccine. “When we grow CVVs in these cell lines however, such changes are rare,” says Professor Barr.
“By using cells instead of eggs, we will improve the number of CVVs we have to choose from and therefore are more likely to be able to match the vaccines to the circulating influenza viruses.”
The paper is a result of a study which began back in 2007 when Novadas Vaccine and Technology asked the team at the WHO Collaborating Centre for Reference and Research on Influenza if they could test their proprietary cell line to see if it could grow influenza virus.
Once the team established they could successfully grow the virus ready for incubation in the chicken egg, the team decided to go one step further, and remove the need for the egg completely.
“It has taken us a while to get to this step, because removing the egg from the vaccine process completely was a bit of a sticking point, however a couple of years ago we finally got the go ahead.” says Peck.
These cell-based vaccines are now available in Australia, but not readily. Cost is a huge prohibiting factor, with cell-based vaccines costing nearly twice as much as those produced in eggs. So, are they more effective?
“We think so, but we need more data to be sure,” says Peck.
“We’re hopeful that as more people take up this vaccine, we will be able to begin analysing their effectiveness in comparison to the traditional egg vaccines, however it could take years until we have concrete evidence.”
In line with this expectation, the UK Joint Committee on Vaccination and Immunisation have made a preferential recommendation for cell-based influenza vaccines over egg-based vaccines for children aged from two years to less than 18 years, and for adults from 18 years to less than 65 years for UK’s 2021/2022 influenza season. No such recommendations have been made in Australia.