Developing a universal flu vaccine requires a two part strategy targeted at the surface of the flu virus and it’s unchanging core
At Last week’s World Vaccine Congress 2014, Vaccine Nation sat down with professor Sarah Gilbertson from the University of Oxford to discuss her progress towards developing a universal vaccine.
What strategy are you currently pursuing in search of a universal flu vaccine?
What we’ve been trying to do is target areas of the flu virus that do not frequently change over time, but that are also well conserved between human, avian and swine flus. If we can use those parts of the virus as our vaccine antigens, in theory we can produce an immune response that protects us against flu even as it drifts in its sequences from year to year, and also if there is a new pandemic, it will protect against the pandemic whether it has come from pig or chickens, or other avian species.
But because those antigens are on the inside of the virus, rather than the surface of the virus, they cannot be reached by antibodies that might be induced through traditional vaccination. So instead we are trying to use the other arm of the immune system, the T-cell response. Whenever people have a flu infection they will develop a T-cell response that will help them recover from that flu infection. The T-cells will attack the virally infected cells and prevent the virus from spreading through the body or prevent the virus being transmitted to another person.
T-cell response is a key part of naturally acquired immunity to flu not induced by traditional vaccines. We know that if a person has recently had seasonal flu then they are much less likely to get pandemic flu when a new pandemic starts. Unfortunately this immunity isn’t very long lasting. What actually happens is that the level of the T-cell response declines reasonably quickly after the flu virus has subsided and they become susceptible again.
So what we’ve been looking at is, first of all, could we boost these T-cell responses using the conserved antigens in the vaccine and a replication deficient viral vector to deliver the antigen. In clinical trials that we have done so far we have found that we can boost those T-cell responses, and they do increase protection against influenza infection.
What we want to find out next is if we can improve the maintenance of these T-cell responses.
Does this technique have the potentially to deliver a truly long lasting flu vaccine?
I don’t ever expect to have a flu vaccine that will be once for life, or 3 doses in childhood and then you’re protected for life. But it would be of use if we were able to have a flu vaccine that did not need to be used every year. Even if we need them just every two years this would mean that for the same number of doses of vaccine we currently use we could vaccinate twice as many people. This would allow us to move towards the aim of universal vaccination (vaccinating the whole population). That’s why it’s important to look at the maintenance of the response.
This is something we are currently doing in a clinical trial where we are using two different viral vectored vaccines (Adenovirus vector and MVA vector), one after the other, in a different order, with different intervals in between the two vaccines, and over time we will look at how well the responses are maintained and contrast them to just using a single vector as we have done so far.
In addition to that, we don’t want to make a vaccine that just works through T-cells, but one that works using antibodies as well. As a first approach towards this goal we have been able to use one of our viral vector vaccines with the traditional trivalent flu vaccine and we’ve seen that when we do this we still get the boosting of the T-cell response, but we also get slightly better antibody responses to the licensed vaccine.
So we have a two-part improvement on the licensed vaccine: we provide a T-cell response, whilst improving the antibody response of the traditional vaccine.
Now that’s not by any means the ultimate universal flu vaccine. But it should be more broadly protective than the current flu vaccine, partly because of the T-cell response, partly because of the improved performance of the traditional vaccine. Also, at the moment, about once in 20 years there is a vaccine failure, where the antigen in that year’s flu vaccine doesn’t match the strain that’s circulating as it’s changed in the year since the WHO determined the strains for that year. The broader coverage of our vaccine should mean we can continue to target flu strains regardless of the yearly drift, avoiding the vaccine failures. This is the first step towards a universal vaccine.
Ultimately there is good agreement between those in pre-clinical development that we are going to need to combine different immune responses against different antigens.