Exploitation of x-ray irradiated viruses for vaccine development (XVacc)

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Many vaccines that have been successfully used for decades have relied on inactivating pathogenic material to render it uninfectious. One benefit of this approach will be the recipients immune system "seeing" the whole pathogen, so the resultant immunity generated will be primed in preparation for exposure to the live pathogen. Other benefits include immunity being generated across a wide array of antigens, rapid scalability, a known safety profile and cost effectiveness.Purified inactivated virus (PIV) vaccines were recently developed for Zika virus, demonstrating protection in animal models including non-human primates and are now entering human clinical trials with US government and commercial support. This work demonstrates that the application of PIV as vaccine candidates remains an important tool for producing rapid and efficacious interventions against pathogenic threats. To date, PIV vaccines are developed using chemical or radiological methods for inactivation; both of which confer severe disadvantages. Addition of inactivation chemicals, such as formaldehyde, risks altering the conformational structure of antigenic targets and compromising the recognition of protective epitopes. Harmful chemical used during the manufacture of vaccines will also need stringent removal before being used for clinical trials adding extra processing, costs and regulatory issues to vaccine development. Whilst gamma irradiation negates the need for chemical intervention, it has a severe limitation with the technology requiring radioactive isotopes for operation. This has financial, environmental, security and moral impacts associated with the use of radiation.X-ray irradiation offers a solution to the production of PIV vaccines by removing the need for radioactive sources to generate beams required to inactivate pathogens. This is a new and emerging technology with huge potential benefits, including being cheaper and secure for direct applications within developing countries. With the benefits of PIV vaccines being exemplified by the recently developed Zika virus vaccine, PHE would use Rift Valley Fever virus to develop a proof-of-concept approach for the use of x-ray irradiated material to generate vaccine candidates. If successful, this approach could be used across different viral pathogens and be highly relevant for responding to emerging health threats as can be rapidly applied to newly isolated viruses that might emerge and threaten human health.