[Monkey Pox] Rapid Research Response
Lead Research Organisation:
University of Oxford
Department Name: Target Discovery Institute
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.
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.
Organisations
People |
ORCID iD |
| Tao Dong (Principal Investigator) |