Select Committee on Science and Technology Written Evidence

Memorandum by the Institute for Animal Health and the Roslin Institute

1.  We will address the question that was posed by the committee: What is the long-term strategy for reducing the threat of pandemic influenza?

  2.  The threat of pandemic influenza in man seems very likely to be related to the level of infection sustained in poultry. Waterfowl are the natural host for avian influenza viruses and it is believed that spread into poultry represents episodic events that may be sustained in the poultry population for varying periods of time. We submit that it is prolonged human contact with infected waterfowl or poultry that increases the risk of pandemic influenza in man - so control in the avian host is critical. Control by depopulation is an obvious option but due to the uncertain nature of pandemic influenza this does not seem viable thus control through alternative means is our focus.

  3.  We propose approaches towards reducing AI in the avian host by:

    -   Generation of novel vaccines and their testing under controlled conditions to enable control of infection during outbreaks of infection;

    -   Screening for differences in the responses of poultry to traditional and new vaccines to promote the breeding of birds with optimal protection following vaccination;

    -   Identification of differences in susceptibility of poultry to influenza virus infection so that it may be possible to breed chickens with a reduced potential for spread of the virus;

    -   Fundamental work to uncover the details of host interactions with avian influenza to give future prospects for control.


  4.  Vaccination is the major method of control for many viruses in the poultry industry, which has experience in developing and administering live and killed viral vaccines. Traditional and new vaccines against avian influenza viruses have mixed success and can cause problems if they result in protection from disease signs and yet fail to block virus transmission.

  5.  Substantial advances in our understanding of the immune response of poultry have been made over recent years with the discovery of genes and proteins that control the immune response. Through our knowledge of these we hope to improve the efficacy of vaccines against avian influenza viruses effective in the avian (poultry) host. Particular discoveries that bear on novel vaccines are the description of proteins that act as molecular adjuvants (such as cytokines and toll-like receptors) to induce the correct immune responses.

  6.  It is not just the genes and proteins that are important to vaccines but vaccines need to deliver the right response to the right place at the right time, and there is increasing knowledge about these parameters. Identification of the right viral proteins, the best vectors, the more appropriate adjuvants, and the best immunisation procedures are crucial for improving the efficacy of vaccination. Another desirable feature of such vaccines would be that they protect against many serotypes, that is to say they are sustainable.

  7.  It is essential therefore that infection of poultry flocks with viruses is determined swiftly, so that timely slaughter and vaccination can be carried out. Masking the infection by vaccination without eliminating shedding of active virus potentially leads to a situation with the virus out of control - as in south east Asia. New vaccines must totally eliminate or reduce shedding to minimal levels to be effective in the long term. New vaccines will need to be developed since there are doubts about the efficacy of current vaccines outside the laboratory environment.


  8.  The management of poultry breeding and production makes it exceptionally well suited to exploiting genetic variants for a useful trait and establishing it in the poultry population; such a trait may be disease resistance. From the field there is little evidence for resistance to avian influenza virus infection since, once established, highly pathogenic strains of avian influenza virus (HPAI viruses) will spread and kill poultry indiscriminately. However this does not imply that all poultry strains are equally susceptible to infection and able to transmit infection. A successful strategy may be to select poultry that (a) need a higher infectious dose of virus or (b) produce less virus when infected. Both strategies effectively reducing the potential of the virus to spread infection and could reduce the risk of pandemic influenza.


  9.  Host genetics may also play a role in the selection of poultry that respond well to vaccination. There is much evidence that different chickens respond differently to various vaccines. In some cases this may be a general trait towards many vaccines and in other cases may be specific for the particular pathogen or vaccine. It is already known that some current AI vaccines efficiently immunise some chickens but not others. The selection by poultry breeding of those genes which allow the best response to the traditional and any novel vaccines is a desirable goal.

  10.  Antiviral innate resistance whether through the interferon system, with its antiviral response, or through other mechanical barriers, is worthy of investigation to be used as part of a suite of traits that could be considered.


  11.  The viruses circulating in poultry and waterfowl in south east Asia are lethal for poultry. It is unusual for such HPAI viruses to be isolated from wildfowl and these strains are a cause of special concern. In infected poultry HPAI viruses are not restricted to replication in the respiratory and alimentary tracts of birds but cause a systemic infection which results in rapid death. How applicable this model is to human infection is not known, but it is clearly a very serious risk factor relating to the severity of the disease. The risks can be considered enormous should the virus acquire the ability to spread to humans more efficiently and then spread from human to human without losing its pathogenic potential. An additional risk might be that the virus does not spread to humans but the pig could act as a source of infection. Even if we get no immediate pandemic, there may be a chronic threat from AI or AI viruses in pigs to transmit to humans, with lethal consequences, and yet still maintaining the potential for starting a future pandemic.

  12.  In the long term, greater understanding of the interactions between the host and avian influenza will be important in our ability to control the spread of this disease. We need answers to questions like:

    -   what factors limit replication and transmission of AI strains within and between different avian and mammalian species?

    -   why are some strains pathogenic in geese and ducks but others are not?

  13.  In recent years the rapid development in genomics and genetics has increased our knowledge of the biology of avian influenza. There has never been a better time to exploit these new tools to increase our knowledge of how the host responds to and may limit avian influenza virus infections. International projects to sequence the genomes of ducks and other hosts will provide information about host defence and susceptibility genes. These sequences will be used to develop the tools to examine host responses in terms of changes in gene expression (­DNA chips") and protein differences (­Proteomics"). The sequence will also be used to screen for genetic variation in host genes and search for associations with susceptibility to infection, and with the ability to shed and spread AI infections.

  14.  Avian influenza is a particularly high-risk virus because it mutates at a high rate and if transmitted to another host species, even at a low rate, may adapt to evolve into a more virulent strain. It is therefore of interest to examine the responses of different host species to avian influenza viruses. Surveillance has detected avian influenza virus strains in a wide range of species, including wildfowl (ducks and geese), shorebirds (gulls and terns), poultry (chicken, turkey, quail) and other birds, mammals (not only pigs, horses, and humans, but also seals, whales, mink, and, more recently, cats and tigers).

  15.  Increased knowledge of the genes and proteins of the host that limit infection may also identify new targets for drugs or vaccine design. Antiviral drugs might therefore be targeted against virus proteins that counter the host antiviral response.

  16.  Finally, the application of novel vaccines, drugs or selected strains of poultry in the field need to be approached with caution. It is important to develop new models of infection at the individual and population level to predict the consequences of their use. Critically, there will be a need to develop infrastructure in additional laboratories to handle the LPAI and HPAI viruses and ensure secure and safe access to these resources. Currently within BBSRC only IAH Compton has facilities to handle highly pathogenic avian influenza viruses, and to our knowledge is one of only five laboratories so equipped and licensed within the UK.

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