الفهرس 
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Abstract
The Caliciviridae comprises a family of related viruses infecting a wide variety of vertebrates including humans. Human pathogens belong to the genera NoV and SaV and induce enteric infections. Of these, the NoVs are by far the most important and account for the bulk of infectious gastroenteritis in adults. Although NoV gastroenteritis is self-limiting, the economic burden is considerable and uncontrolled manifestations can result in severe dehydration and possibly death.
Noroviruses form an antigenically diverse group of agents and cross reactive immunity is poor. These features present a considerable challenge for vaccine development, but approaches have been based around the use of empty VLPs produced by self-assembly of the virus capsid protein. Such structures have been delivered by conventional means to control animal infections, but the formation of a stable particle that can withstand passage through the gut has raised the possibility of enteric immunization via edible vaccines and this approach has shown promising results in some systems.
This study addressed these issues by attempting to engineer stable particles of Hawaii virus capsid protein that induces more broadly cross reactive antibody by deleting those immunodominant regions that evoke type-specific responses. Those constructs were expressed using the baculovirus system and the results obtained support the concept that bridging the gap with polyglycine amino acid chains where the hypervariable region had been removed was permitting some form of structural assembly including ring form and VLPs. In an attempt to improve the protein yield we changed the expression system to yeast which showed a better expression level of the engineered proteins that could be purified.
To evaluate such particles as potential carriers of antigenic domains from unrelated viruses, part of the HA domain of influenza ‘A’ virus was carefully selected to replace the polyglycine chain and this construct was also expressed in yeast.
All expressed protein constructs were administered in dried whole yeast cells orally to mice in an attempt to evoke a local immune response, while the purified proteins were used as controls for intravenous immunization of mice to confirm the induction of systemic immune response.
In this study, it has been possible to determine immune reactivity towards the engineered Hawaii VP1 which may indicate potential for greater response if administration could be prolonged. Analysis of reactivity towards influenza HA segment included in the engineered Hawaii-Hemagglutinin chimeric protein is clearly of interest and can be considered in future work.