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Making Vaccines More Effective

24 -30th April each year is the World Health Organisation World Immunization Week. To mark this occasion, NDM spoke to Professor Simon Draper, a MRC Career Development Fellow based at the Jenner Institute, about making vaccines more effective.

Professor Simon DraperProfessor Simon DraperQ: How does a vaccine work?

Simon Draper: A vaccine relies on the remarkable ability of the immune system to recognise what it has seen before – we call this process immunological memory. A vaccine is a bit like a photograph – when the vaccine is injected in to the body it provides a picture of the pathogen. It forewarns the body of something that is bad so if that pathogen is then encountered in the future the immune system will remember it and can respond to it appropriately.

Q: How can you make a vaccine more effective?

SD: There are lots of different ways that scientists can try and make a vaccine more effective. Vaccines are made up of multiple components and by altering these different components we can try and improve how effective a vaccine is.

One of the components of a vaccine is part of the pathogen, or infectious organism, that you are interested in generating an immune response against. Normally, this is a protein but in some instances it could also be a sugar. Another part is the delivery system, which is normally the bit of the vaccine that stimulates the immune system to respond. Therefore to make a vaccine more effective, you want to make the delivery system as effective as possible to increase the immune response to the protein which is injected in the vaccine.

One of the leading approaches that has been developed in Oxford is to use viral vectored vaccines to make vaccines more effective. This approach uses recombinant viruses to produce the protein of interest without the virus being able to replicate. Because the body has evolved to know that a virus is usually dangerous, the immune system will respond not only to the virus but also to the protein from the pathogen at the same time. We use two different viruses in a ‘prime-boost’ approach to do this. The first virus is normally an adenovirus to ‘prime’ the immune response and the second virus is usually a poxvirus to ‘boost’, leading to the induction of high levels of antibody. Both of these viruses encode the same protein, aiming to generate as protective an immune response as possible against this target. This approach has shown a lot of promise in laboratory studies and has now been used in numerous clinical trials for malaria, tuberculosis, HIV, flu and, most recently, for Ebola.

Crystal structure of the Plasmodium falciparum RH5 proteinCrystal structure of the Plasmodium falciparum RH5 proteinThere are other ways that we can try to make vaccines more effective. We can improve the way that the immune system responds to the protein by including an adjuvant – a chemical formulation that stimulates the immune system. Another possible way of making a protein more immuno-stimulatory is to make it in to a “virus-like particle”. This is an array, a bit like a football with lots of proteins sticking out the surface. Because this array looks like a virus (it’s the right shape and size) in many cases the immune system will generate a strong antibody response against the array.

Q: How is your research improving vaccine design?

My research is primarily focused on developing vaccines against the blood-stage of malaria. In my case, we use a protein from the malaria parasite to generate a protective immune response against the disease.

Malaria proteins can be pretty large and rather than trying to generate an immune response to the whole protein we have found that only certain bits of the protein are important for generating the immune response. When we vaccinate people in our clinical trials against malaria we carefully characterise the antibody response to the injected proteins and we look at what types of antibodies people make when we vaccinate them. We can then look at the structure of the protein to see where these antibodies bind. We also know from data from the trials whether the antibodies generated are able to kill the malaria parasite. By doing this work we can figure out which antibodies are important and where they stick to that protein. We can then use this information to feed back in to our vaccine design process and redesign the protein to try and focus the immune response on those most important parts. This work using protein structures is now a leading approach in vaccine design as it tries to improve vaccines so that they give a very focused and effective response.