Genetically engineered structure-based vaccine for bluetongue disease.
At present the only vaccines used against bluetongue (BT) disease are live-attenuated virus vaccines. Since viruses with RNA genomes such as BT virus (BTV) have a high frequency of mutations, live virus vaccines could have breakthroughs (vaccine failures) and mutate into virulent strains. In addition, multiple BTV serotypes exist in nature which could potentially cause additional problems with live virus vaccines. The BTV genome is made up of 10 segments and therefore potentially could exchange these segments (or genes) randomly between different viruses including vaccine strains, generating novel viruses with mixed genes. Hence it is necessary to develop BTV vaccines that pose no such threat. Ideally BTV vaccines should be completely devoid of harmful genes. Recent protein expression technology has provided novel approaches for the development of intrinsically safe vaccines. The technology involves the synthesis of immunogenic proteins and particles that elicit highly protective immune responses. We have generated such vaccines, termed virus-like particle (VLP) vaccines. These vaccines (which do not carry either BTV or foreign genes) give the immune system information about viral structures so that it can generate a complete defence against the real virus infection very efficiently. A series of vaccine trials were undertaken outdoors under natural UV light using 50-200 BTV-susceptible sheep per trial. Vaccination trials of sheep showed that the VLPs were highly immunogenic, and protected sheep when animals were challenged with virulent virus even 15 months after the first immunisation. Moreover, a cocktail of five VLPs afforded protection against not only each of the homologous BTV serotypes but also against certain heterologous serotypes that are genetically related to some of these vaccine strains. VLPs representing a number of serotypes are currently available and can be produced fairly quickly if there is such a need. Based on our sequence data it can be predicted that a mixture of seven or eight types of VLPs (that are already available) will provide protection against at least 10 or more serotypes depending on their phylogenetic relationships. BTV VLPs offer particular advantages as potential vaccines over other systems. Large quantities of VLPs can be produced and easily purified using a one-step protocol based on the physical properties of the particle. More importantly, these particles are devoid of any nucleic acid and thus pose no threat by re-assortment or the re-emergence of virulence that attenuated vaccines can cause.
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Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.