Antigenic properties of single-cycle influenza viruses

The influenza virus is a common pathogen in avian, swine and human populations. While some strains of influenza cause only mild pathology, others are highly pathogenic and pose a significant pandemic threat. Vaccines available for seasonal influenza are highly strain-specific, take a long time to produce and are unsuitable for use in pandemics. Non-replicative influenza viruses can be produced by inactivating one or more of the genes in the influenza genome. Replication-permissive cell lines can be produced which provide a functional form of the relevant protein in trans and hence compensate for this loss. Such a system allows the production of viruses which are able to undergo only a single replication cycle when grown outside of this permissive environment. Studying the antigenic properties of these viruses as well as their ability to induce protective immune responses in vivo could highlight single-cycle influenza viruses as potential vaccine candidates for influenza. Previous work has shown that single-cycle viruses based on the inactivation of the hemagglutinin signal sequence induce strongly protective T-cell responses, but only very weak antibody responses towards hemagglutinin due to its reduced expression. The present project aims to build on this by generating viruses that produce a non-functional hemagglutinin which is expressed at the cell surface, and testing the ability of these viruses to protect against challenge with wild-type influenza virus in mice, ferrets, birds and pigs. This work could lead to the development of a novel broad-spectrum vaccine suitable for seasonal and pandemic influenza in a wide variety of species.

The proposed project addresses the following BBSRC areas of interest:
Animal health- The development of an effective influenza vaccine would protect the health of susceptible animal species, both farmed and wild.
Welfare of managed animals- Influenza currently impacts on the welfare of farmed pigs and birds, for instance by causing weight-loss and fever, and spreads quickly through managed animals.
Global food security- Influenza infection reduces the quality and quantity of animal products available for human consumption. A large proportion of human caloric intake is associated with the consumption of products from animals susceptible to infection with influenza. Large scale outbreaks in managed bird populations are of particular concern.
In vivo techniques- Efficacy studies for a potential vaccine candidate require appropriate training in animal handling for experimentation.

AFS, BfH, ENWW