Library of potential pandemic vaccine reference viruses and reagents

An influenza virus needs to meet two criteria in order to cause a pandemic; it needs to be new, i.e. the human population must be immunologically naive to the given virus, and it needs to be able to transmit easily between humans. Whereas the first criterion applies to the highly pathogenic avian H5N1 viruses currently found in parts of Asia, Africa and Europe (Areas with confirmed human cases of H5N1 avian influenza since 2003 ), ( Areas reporting confirmed occurance of H5N1 avian influenza in poultry and wild birds since 2003 ), ( Update on highly pathogenic avian influenza in animals ), they have not acquired the capability to spread efficiently between humans. Pandemic preparedness efforts around the world are focussed mainly on these avian H5N1 viruses. However, it is impossible to predict whether or not these viruses will change so that they can easily transmit between humans.

Avian influenza viruses in reality comprise a vast array of different viruses of different subtypes. Aquatic birds are the natural reservoir for influenza A viruses and all subtypes described so far (H1 – H16 for the haemagglutinin (HA) and N1 – N9 for the neuraminidase (NA)) can be found in birds. Only viruses of the subtypes H1N1, H2N2 and H3N2 are known to have become pandemic, and subsequently, epidemic for humans. Therefore, most influenza viruses found naturally are “novel” to the human immune system and thus fulfil the first criterion for pandemic potential. As is the case for H5N1 viruses, we cannot predict which avian viruses of any subtype may acquire properties that allow infection of and spread between humans. However, we know that some avian viruses have caused sporadic human or mammalian infections, so in terms of pandemic preparedness, these viruses should not be neglected.

One of the major interventions in the case of a pandemic will be the use of vaccine. Such vaccines will be needed very quickly, yet we envisage that it would take several months to produce a pandemic vaccine. In a pandemic emergency, it is therefore likely that vaccine would not be available for the first wave of the pandemic. If, however, suitable candidate vaccine viruses are already available at or before the onset of a pandemic, the response time will be shortened.

We have embarked on a project to create a “library” of candidate vaccine viruses and associated Single Radial Diffusion (SRD) reagents for various avian subtypes. Our focus initially is on “high-risk” subtypes of influenza A virus, as described by WHO and others (Wood and Robertson, 2007). These are subtypes that are known to have infected humans or other mammalian species, such as the H5, H7, H9, H2, H6, and H4 subtypes. The ultimate goal however, is to create a library covering all known subtypes of avian influenza.

One of the potential drawbacks of a library approach is the fact that we cannot predict which virus may become pandemic in the future. Thus, the candidate vaccine viruses contained in the library will almost certainly not be perfectly matched to the virus actually causing the pandemic. How do we overcome such drawbacks?

• We can make sure that library viruses are antigenically representative of viruses prevalent in bird populations worldwide. We have established collaboration with Drs Derek Smith and Ron Fouchier at the University of Cambridge, Cambridge, UK, and MC Erasmus, Rotterdam, Netherlands, respectively, to use antigenic cartography (Smith et al., 2004) in selecting candidate vaccine viruses.
• We can evaluate the immunogenicity and protective efficacy of library vaccines in preclinical studies.

Once we have chosen a strain representative of a subtype or a group (cluster) of viruses within a subtype, a candidate vaccine virus will be made by classical reassortment with the high-yielding strain PR8 or by using reverse genetics. Alternatively, we may use a wild-type virus as a candidate vaccine virus if it is of low pathogenicity and grows well. In addition, the library will contain an antigen reagent and an antiserum reagent for each vaccine strain to be used for standardisation of vaccine by the SRD assay.

Our work on establishing a library of vaccine reference viruses and associated reagents has been funded in the past by the European project FLUPAN and is currently funded in part by the European project FLUSECURE (NIBSC site and FLUSECURE site).

Click here to view our current list of viruses and reagents in our library, which interested parties may obtain upon request ( Table ).

References:

J. M. Wood, J. S. Robertson. Reference viruses for seasonal and pandemic influenza vaccine preparation. Influenza (2007); 1: 5–9.

D. J. Smith, A. S. Lapedes, J. C. de Jong, T. M. Bestebroer, G. F. Rimmelzwaan, A. D. M. E. Osterhaus, R. A. M. Fouchier. Mapping the Antigenic and Genetic Evolution of Influenza Virus. Science (2004) 305: 371-376, 2004.