In spite of the recent outbreak of Ebola and then Zika, many governments still believe that influenza is the virus most likely to bring the world to its knees. But why? It is cunning – changing its coat every year, it can undergo rapid international travel carried by migratory birds as well as by airline passengers and it also infects domesticated farm animals (chickens and pigs) that live at the side of millions of people around the world. The Spanish flu of 1919/1920 provides stark evidence of the danger as this flu virus managed to kill more people than WWI!
The good news is that there is an effective flu vaccine available and companies are able to make sufficient doses to meet the needs of national vaccine plans. However, in order to produce the vaccine each year the world relies on a small network of scientists, who ensure that the companies have all the right materials to produce the millions of doses of vaccine. This small group that are the lynchpin in flu vaccine production, includes a team of scientists from the Influenza Resource Centre at NIBSC.
Influenza is a global disease and although, in any one country, it is a disease of winter, from a global perspective it occurs all year round, moving from Southern Hemisphere to Northern Hemisphere countries as the seasons progress. To enable the world to respond, the World Health Organisation coordinates a global network of laboratories (GISRS – Global Influenza Surveillance and response System) with a group of 6 laboratories (called WHO collaborating centres for influenza) at its core that track the virus. They monitor the isolates associated with disease from every country and look to see whether the flu vaccine needs to change in order to protect against the currently circulating virus. Deciding whether the vaccine needs to change is a difficult process and requires considerable skill to predict what will happen in the 6 months it takes for the manufacturers to make sufficient vaccine ready for next winter.
Once the decision is made on what flu strains the vaccine should contain, then it is up to another 4 labs in this WHO network (called Essential Regulatory Labs) to prepare and supply the manufacturers with the candidate vaccine viruses (CVVs) that are used for all the vaccine production worldwide. As well as the CVVs, the Essential Regulatory Laboratories produce additional reagents that are critical in assuring the quality of the vaccine produced and that each vaccine contains the right dose.
The flu team at NIBSC is one of the 4 Essential Regulatory Laboratories (ERLs), but it is one of the busiest, supplying request s to flu vaccine manufacturers from the largest number of countries around the world. Making the materials that assure vaccine quality is not straightforward and time dependent and sometimes things get a little fraught. Nevertheless, the team at NIBSC have an enviable record not only dealing with regular years where every ERL successfully contributes to the process, but also helping other ERLs when issues arise or extra resource and work are required
This tightly scheduled process ensures that vaccines are available for the old and those with underlying respiratory conditions who are put at greater risk from seasonal flu. But what happens when a completely different PANDEMIC strain comes “out of the blue”, as was the case in 2009? These completely different flu strains have appeared approximately once every 20-40 years and they pose an increased threat in the world as virtually no-one has immune protection. This makes more people susceptible to infection and severe disease. In a pandemic, more vaccine is needed and there is less time to make it. Adding to these problems, the new pandemic flu strain will have to be handled in special laboratories, under stricter bio-containment, making it harder to produce the safe vaccine strain by conventional methods. Fortunately, a new molecular genetic method for producing recombinant vaccine viruses has been developed and the team at NIBSC routinely practice this process, with the goal of producing candidate vaccine viruses ready for the manufacturers within 19 days of getting the pandemic virus. These practice runs are frequently performed using strains which are highly virulent, but fortunately have not gone on to establish human to human transmission. Each of the strains added to this “library” of CVVs may provide a source for a pandemic vaccine in the absence of a perfect vaccine match.
As well as ensuring that the CVV contains the best vaccine match for the circulating flu strain, producing a vaccine virus that grows really well in large scale production at manufacturers could be critical. Halving or doubling the amount of material coming out of these facilities could be the difference between having enough vaccine for everyone. To overcome this problem, the team at NIBSC are working with molecular virologists from the Roslin Institute near Edinburgh. Their goal is to modify parts of the vaccine virus backbone in such a manner that there should be enough vaccine produced irrespective of the virus strain needed to protect people from disease.
So next time you see an advert inviting you to get protected against flu, there is a reasonably high chance that the vaccine you will get would not have been available without the help of a small group of scientists working in South Hertfordshire.