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Monkeypox Rapid Research Response

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary, Life Science

Abstract

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Technical Summary

The 200 kb MPXV genome is a challenging sequencing target due to repeated sequences near each genomic terminus and low GC (33%) content. A fast, reliable and low-cost method will be developed that can accurately reconstruct the genome for evolutionary analysis, genomic epidemiology and functional character-isation.
A panel of cell lines from a range of rodent and livestock species available at Pirbright will be used to examine the host range of MPXV. Virus growth in cell culture will be measured using classical methods and live-cell analysis systems.
We will determine MPXV evolution of tropism and hIFN-I antagonism, to predict virus human-to-human transmission.
We will evaluate the long-term immunity induced by MPXV infection in humans and define differences between vaccine-induced responses: immunodominance pattern, functional immunophenotype and if T cell responses to MPXV viral immediate early proteins exhibit better viral control than other specificities. Also, associations with antibody responses and clinical outcome will be evaluated.
We will establish and optimise antiviral screening pipelines to assess the antiviral efficacy of tecovirimat and brincidofovir, drugs with known activity against orthopoxviruses. We assess 26 FDA-approved drugs and a novel cyclosporine A derivative that inhibit VACV in vitro. Also, current MPXV isolates will be tested in cell culture for the rapid testing of circulating strains of MPXV for tecovirimat-resistance.
We will develop two rapid point of care diagnostic tests. Lateral flow Assay (LFA). An orthopoxvirus (OPV) LFA has been developed at Dstl, comprising 4 Mabs all reactive with old world OPVs. Making use of novel bead types we will provide data packs to enable rapid progress through regulatory pathways for licensure.
Loop-mediated isothermal amplification (LAMP)-based assay. LAMP is a rapidly maturing technology providing PCR levels of sensitivity and specificity without the need for thermal cycling.
 
Description Setting up of collaborative network.
Development of pipeline to test anti-viral compounds against mpox.
Development and sequencing of clinical strains of mpox.
Identified compounds inhibiting mpox replication.
Development of organoid skin cultures for mpox.
Correlation between temperature elevation and type-I IFN-mediated restriction of mpox.
Development of collaboration with industry partner, that includes current joint funding applications.
Exploitation Route Develop technological tools, reagents and techniques to study mpox.
New UK-wide collaborations on mpox.
Anti-viral pipelines available for the community.
Sectors Healthcare

Pharmaceuticals and Medical Biotechnology
 
Description This award supported rapid scientific investigation of the mpox outbreak and generated new insights into immunity, virus biology and potential antiviral strategies for poxvirus infections.Supporting NHS for identification of drug resistance mpox strains in patient samples. A key impact of the work was improving understanding of population-level immunity to mpox virus. Studies associated with this award demonstrated that individuals who received childhood smallpox vaccination retain measurable immune responses that can provide cross-reactive protection against mpox virus infection. Subsequent work further characterised adaptive immune responses to mpox infection, including T cell memory responses and their functional properties, improving understanding of how immune protection develops following infection or vaccination. The award also supported clinical and virological studies that helped clarify the dynamics of mpox infection in patients. Isolation of mpox virus from longitudinal clinical samples provided important information about viral replication and shedding in infected individuals, helping inform understanding of disease progression and transmission. In addition to immunological studies, the programme explored potential antiviral strategies against poxviruses, identifying compounds capable of inhibiting replication of prototype and emerging poxviruses. These findings contribute to broader efforts to identify therapeutic approaches that could be deployed during future outbreaks involving mpox or related viruses. Overall, the work generated new knowledge relevant to public health preparedness for poxvirus outbreaks, including insights into immune protection, population susceptibility and potential therapeutic targets. By combining immunological, virological and clinical research approaches, the project contributed to the scientific evidence base needed to inform responses to emerging mpox outbreaks and future orthopoxvirus threats.
Sector Healthcare
Impact Types Policy & public services
 
Description Media engagement for Mpox 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Emma Thomson was featured on Sky evening News talking about how the Mpox which was in the UK in 2022 is different to the Mpox clade II that is currently endemic is Africa.
Year(s) Of Engagement Activity 2024
URL https://news.sky.com/video/how-does-mpox-spread-and-what-risk-does-it-pose-to-africa-and-the-rest-of...