Analysis of cytomegalovirus pathogenesis in a human challenge system (360G-Wellcome-204870_Z_16_Z)

£2,669,767

Our research has made major contributions to understanding the natural history and pathogenesis of human cytomegalovirus (HCMV) in allograft recipients. Critically, we have demonstrated that biomarkers can be applied to stratify patients most at risk of HCMV disease and thus inform clinical practice to reduce HCMV end-organ disease. This clinical approach of administration of antivirals to individuals with elevated viraemia above designated levels provides a unique opportunity to gain fundamental insight into disease processes in a human challenge model of HCMV infection. A multi-disciplinary consortium has been recruited to apply next generation DNA sequencing, molecular virology and functional immunological assays to identify virus and host cell determinants of disease susceptibility. Whole genome sequencing of virus in organ donors (live and cadaveric) and recipients will be used to track the source, replication kinetics and evolution of HCMV strains in seronegative and seropositive recipients. We will then define in vitro humoral, cell-mediated immunity and natural killer responses against HCMV that correlate with protective immunity against primary infection, reinfection and reactivation in these patient groups. This approach has the potential to provide unique insights into the natural history and pathogenesis of HCMV and identify innovative therapeutic approaches against it.

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Grant Details

Amount Awarded 2669767
Applicant Surname Griffiths
Approval Committee Science Interview Panel
Award Date 2016-11-30T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Collaborative Award in Science
Internal ID 204870/Z/16/Z
Lead Applicant Prof Paul Griffiths
Other Applicant(s) Dr Mark Wills, Dr Matthew Reeves, Prof Andrew Davison, Prof Gavin Wilkinson, Prof Judith Breuer, Prof Richard Stanton
Partnership Value 2669767
Planned Dates: End Date 2023-04-03T00:00:00+00:00
Planned Dates: Start Date 2017-04-03T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London