Monkepox Rapid Research Response
Lead Research Organisation:
University of Surrey
Department Name: Microbial & Cellular Sciences
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.
Publications
Laidlaw S
(2025)
Detection of mpox and other orthopoxviruses using a lateral flow device as a point-of-care diagnostic
in Microbiology Spectrum
Ndodo N
(2023)
Distinct monkeypox virus lineages co-circulating in humans before 2022.
in Nature medicine
| Description | Monkeypox virus (MPXV) is a rodent zoonotic orthopoxvirus (OPXV) that has recently emerged globally with unprecedented human-to-human transmission. In 2022, MPXV clade IIb (lineage B) caused a global outbreak. Lineage B is phylogenetically linked to West African endemic viruses with lower transmissibility (lineage A). This suggests that despite its rodent origin, lineage B has adapted to infect, and transmit amongst, humans. We hypothesised that MPXV lineage B has evolved to defeat human host defences more effectively than lineage A, hence explaining its capacity to spread globally. Using a comparative virology approach, we have shown that both endemic and global MPXV effectively suppressed human antiviral innate immunity, with a major role for a viral protein termed poxin. Despite this evasion, human cells recognised MPXV infection and mounted an inflammatory response. Surprisingly, lineage B was less effective in bloking human defences, possibly explaining why this lineage is reportedly less aggressive than lineage A. This was confirmed in animal model of infection, where B caused fewer signs of disease than A. Finally we have identified a compound termed diABZI with extremely potent activity against MPXV, particularly in macrophages. |
| Exploitation Route | The findings reveal differences between MPXV lineages, demonstrating this virus is evolving and may result in new variants if not eradicated. The findings pose questions on how virus attenuation and host inflammation affect transmissibility of poxviruses, hence providing understanding on virus pandemic potential and preparedness since MPXV endemic in Africa is still virulent and future outbreaks may show higher morbidity and mortality than what expected based on the 2022 global outbreak. The findigs also open the possibility of a new host-directed therapeutic approach based on ABZI drugs and derivatives. We are in the process of understanding how MPXV is recognised by our cells to activate an inflammatory resonse and whether this response effectively curtails virus activities and replication. We are also exploring MPXV evolution and drug development in collaboration with others. |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | Monkeypox virus evolution |
| Organisation | Defence Science & Technology Laboratory (DSTL) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | This collaboration has given us access to different virus species to do comparative virology and evolutionary studies. |
| Collaborator Contribution | Contributed viral species and intellectual input to yield new insights onto the evolution of currently circulating monkeypox virus and other poxvirus species. |
| Impact | This is a multidisciplinary collaboration that involves virologists, bioinformatics and computational biology. Outcomes: publication Ndodo et al. (2023) Nature Medicine. |
| Start Year | 2023 |
| Description | Monkeypox virus evolution |
| Organisation | Public Health England |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | This collaboration has given us access to different virus species to do comparative virology and evolutionary studies. |
| Collaborator Contribution | Contributed viral species and intellectual input to yield new insights onto the evolution of currently circulating monkeypox virus and other poxvirus species. |
| Impact | This is a multidisciplinary collaboration that involves virologists, bioinformatics and computational biology. Outcomes: publication Ndodo et al. (2023) Nature Medicine. |
| Start Year | 2023 |
| Description | Mpox diagnosis - Antigen Tests, Oxford |
| Organisation | University of Oxford |
| Department | Medical Sciences Division |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My team tested and validated an Mpox antigen test developed by the Oxford team. We are one of the few research groups in the UK with know-how and access to work with live monkeypox virus, and we validated the Oxford test using 2 different viral strains. |
| Collaborator Contribution | The team in Oxford designed and developed the prototypic test and supplied them to us for experimental validation. |
| Impact | The collaboration has yielded one publication (Laidlaw et al., 2025 - doi: 10.1128/spectrum.02456-24). |
| Start Year | 2023 |
| Description | Mpox diagnosis - Molecular Tests, Imperial |
| Organisation | Imperial College London |
| Department | Department of Infectious Disease |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My team contributed to the development of a molecular test for mpox detection. We are one of the few groups in the UK with the know-how and access to work with live monkyepox virus. We tested procedures to inactivate the virus and validated the specificity and sensitivity of the molecular device using two different strains of the virus. |
| Collaborator Contribution | The team at Imperial designed and developed the molecular test. |
| Impact | The collaboration has yielded a publication that has been accepted in the journal Nature Communications (currently in press). |
| Start Year | 2023 |
| Description | Quantitative proteomics |
| Organisation | University of Cambridge |
| Department | Department of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My team carried out experiments with live monkeypox virus as well as related viruses to complement proteomics studies performed at the University of Cambridge. |
| Collaborator Contribution | The team in Cambridge carried out quantitative proteomics experiments to identify interactions between human cells and the monkeypox virus, the mpox aetiological agent. |
| Impact | This collaboration has not resulted in any output yet. |
| Start Year | 2023 |
| Description | Catalan Society for Virology |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | Delivered Opening lecture at the Annual Catalan Society for Virology meeting as world-leading expert on monkeypox virus. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Daily Mail July 2022 |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Quoted as poxvirologist expert by newspaper Daily Mail on the evolution of the global monkeypox outbreak declared in May 2022. |
| Year(s) Of Engagement Activity | 2022 |
| Description | El Pais July 2022 |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Quoted as poxvirologist expert by Spanish newspaper El Pais on the global monkeypox outbreak declared in May 2022. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://elpais.com/sociedad/2022-07-12/europa-amplia-la-vacunacion-contra-la-viruela-del-mono-a-las-... |
| Description | El Pais September 2022 |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Quoted as poxvirologist expert by Spanish newspaper El Pais on the evolution of the global monkeypox outbreak declared in May 2022. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://elpais.com/sociedad/2022-10-01/los-contagios-de-la-viruela-del-mono-en-el-mundo-caen-a-la-mi... |
| Description | El Pais September 2023 |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Interviewed by largest Spanish newspaper El Pais on evolution and eradication of Mpox in Europe. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://elpais.com/sociedad/2023-11-16/asi-renuncio-europa-a-eliminar-la-viruela-del-mono-sera-una-e... |
| Description | Lancaster University |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | About 50 individuals from the Institute attended an invited talk on virus immunity and vaccines that was well received. |
| Year(s) Of Engagement Activity | 2023 |
| Description | My University newspaper July 2022 |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Wrote an educational piece on monkeypox virus for the University community. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Pirbright Institute |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | Delivered a seminar on the emergence and evolution of monkeypox virus and the 2022 global outbreak |
| Year(s) Of Engagement Activity | 2024 |
| Description | Reuters July 2022 |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Quoted as poxvirologist expert by main news agency Reuters on the evolution of the global monkeypox outbreak declared in May 2022. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.reuters.com/business/healthcare-pharmaceuticals/eu-drugs-regulator-beefs-up-monkeypox-re... |
| Description | Roslin invited seminar |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | About 100 individuals from the Institute attended an invited talk on virus immunity and vaccines that was well received. |
| Year(s) Of Engagement Activity | 2023 |
| Description | The Guardian August 2022 |
| 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 | Public/other audiences |
| Results and Impact | Quoted as poxvirologist expert by newspaper The Guardian on the evolution of the global monkeypox outbreak declared in May 2022. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.theguardian.com/world/2022/aug/15/smallpox-vaccines-protect-monkeypox-hiv-erode |