Institute: MRC Unit The Gambia at LSHTM
Exploring mucosal molecular signatures associated with successful challenge with live attenuated influenza viruses
Live attenuated influenza vaccines (LAIV) contain weakened versions of flu viruses, which can infect people, but do not cause severe illness. Although primarily used for vaccination, they are also safe to be used as surrogate challenge viruses to test how well other new vaccines work. This will be particularly useful in children, where LAIV is known to be very safe, but ‘wild-type’ flu virus challenge models are not ethically justifiable. As such they are potentially a useful model to accelerate influenza vaccine development in children globally.
In this project, we aim to gain insight into what genetic elements in individuals given the vaccine determine whether nasal challenge with a live attenuated influenza virus is successful in causing infection. We will do this in UK adults and Gambian children.
To gain a detailed understanding of how attenuated influenza viruses interact with our immune system, samples for laboratory studies need to be taken from the site of infection (i.e. the nose and related areas). In studies involving volunteers, getting suitable samples in a non-invasive way can be challenging. Our studies have shown that although we can acquire genetic material (‘RNA’) from non-invasive methods such as swabs, it is often not of sufficient quantity and quality to use with currently available standard laboratory methods.
To achieve the aims of this project, we will develop establish new laboratory methods to use with non-invasive nasal sampling. This will allow us to gain insight into how influenza viruses interact with our immune system at the site of infection in a more detailed way than previously possible. These methods will not only be useful in the context of LAIV studies to accelerate vaccine development, but also more widely for other challenge agents given via the nose.
More about Dr De Silva here.