Ian Jones
School of Biological Sciences, University of Reading, U.K.

Recombinant proteins are a safe and rapid route to the development of a number of potential vaccines but are often poorly immunogenic or difficult to produce. In influenza for example, although recombinant haemagglutinin (HA) protein, the principle target of neutralizing antibody, has been shown to be well tolerated and effective it requires larger doses than conventional split vaccines to achieve protective antibody titers. In Foot and Mouth Disease (FMD) a simple recombinant protein approach is ineffective and the structure of the virus capsid is required for effective immunity although it is difficult to produce. We have explored the potential for improving recombinant sources of antigen through tagging with immunoactive fusion partners or by assembly of virus like particles following expression in inset cells.
In influenza, the addition of the human Ig Fc domain, previously shown to enhance immunogenicity through immune targeting or improved half-life, to the C-terminus of H1, H3 or H5 haemagglutinins resulted in the expression of a functional fusion protein, HA-Fc, which is easily purified, oligomeric and generated good antibody titers in the absence of adjuvant that included neutralizing antibodies.
In the case of Foot and Mouth Disease, virus like particles, empty capsids, were assembled efficiently through the expression of novel constructs which linked the P1 structural protein precursor with a modified 3C protease. Control of 3C activity was essential for efficient synthesis and empty capsid assembly was demonstrated for both A and O serotypes. Empty capsids were immunogenic in cattle and protected against FMDV challenge.