Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses
Lead Research Organisation:
Animal and Plant Health Agency
Department Name: Virology
Abstract
High pathogenicity avian influenza virus (HPAIV) is a significant burden on animal health, with a risk of human infection that demands continuous monitoring and control globally. Incursions of HPAIV into the UK and Europe have increased significantly in the last two winter seasons. During the 2020/21 season, 26 infected poultry premises (IPs) were detected across the GB (24 IPs) and NI (2 IPs) with over 300 wild birds testing positive, a record outbreak season at that time. The 2020/21 outbreak was dominated by the detection of the HPAIV H5N8 subtype, although an undercurrent of alternative H5 based subtypes was detected including H5N5 in poultry, and H5N1 and H5N3 also being detected in wild birds. This season was then followed by a significant escalation in cases due to new incursions during 2021/22, with over 100 IPs across the UK, all caused by H5N1 HPAIV. During 2021/22, more than 800 wild birds have tested positive for H5N1 virus, with just a single wild bird detection of H5N8. This project targets this extreme emergence of HPAIV in the UK (and beyond), to improve our understanding of HPAIVs to help mitigate incursions and refine approaches to future prevention strategies.
Work-package (WP1) aims to improve the understanding of HPAIV transmission dynamics for these viruses in both wild birds and domesticated poultry. By undertaking biological sampling and data analysis we will design more effective, risk-based surveillance programmes and model interactions at wild bird and poultry interfaces, defining geographical sites and wild bird populations of high risk, and linkages to farm incursions. Outputs will enable a greater understanding of the reservoir of infection, wild waterfowl, as well as factors that drive incursion of disease from this reservoir into the poultry sector.
WP2 aims to assess antigenic diversity across the HPAIVs detected in the UK in recent years in context of co-circulating low pathogenicity AIVs, in the absence of disease, both in wild waterfowl and poultry. The sequential emergence of HPAIVs suggests that prior immunity from 2020/21 to H5N8 virus was insufficient to prevent emergence and dominance of H5N1 during 2021/22. This WP will define how antibody responses to different virus surface proteins impact upon the potential of virus emergence. This feature of infection will utilise post-infection antisera derived from natural and experimental infection to study immune escape. Areas of the virus that are identified as being important in the emergence of escape mutants will be further investigated to define where flex exists within viral proteins targeted by the host immune response. This will enable focused studies that will help develop our understanding of what factors might influence future mitigation strategies.
Finally, factors that drive differential disease outcomes, outside of the viral surface proteins, will be assessed in WP3. Here, novel systems will be developed to assess viral infectivity and host range which in turn will enhance our understanding of virus-host interactions and define the role of internal viral proteins, critical to viral replication, driving virus diversity and emergence with consequent disease outcomes. WP3 will utilise outputs from WP1 and WP2 to examine the mechanisms that drive the emergence of virus variants, enabling differential adaptation to different hosts. Experimental systems that enable individual components of the viral replicative machinery to be assessed and compared will be developed, utilising our ability to generate viruses in the laboratory to defined genetic specification. Minimal infectious doses and related growth kinetics will be assessed to refine work in animal models. Utilising expertise from across the UK in different experimental systems, with access to a range of laboratory facilities, the partners will link across WPs to generate impactful outputs to enhance our understanding of these emerging pathogens.
Work-package (WP1) aims to improve the understanding of HPAIV transmission dynamics for these viruses in both wild birds and domesticated poultry. By undertaking biological sampling and data analysis we will design more effective, risk-based surveillance programmes and model interactions at wild bird and poultry interfaces, defining geographical sites and wild bird populations of high risk, and linkages to farm incursions. Outputs will enable a greater understanding of the reservoir of infection, wild waterfowl, as well as factors that drive incursion of disease from this reservoir into the poultry sector.
WP2 aims to assess antigenic diversity across the HPAIVs detected in the UK in recent years in context of co-circulating low pathogenicity AIVs, in the absence of disease, both in wild waterfowl and poultry. The sequential emergence of HPAIVs suggests that prior immunity from 2020/21 to H5N8 virus was insufficient to prevent emergence and dominance of H5N1 during 2021/22. This WP will define how antibody responses to different virus surface proteins impact upon the potential of virus emergence. This feature of infection will utilise post-infection antisera derived from natural and experimental infection to study immune escape. Areas of the virus that are identified as being important in the emergence of escape mutants will be further investigated to define where flex exists within viral proteins targeted by the host immune response. This will enable focused studies that will help develop our understanding of what factors might influence future mitigation strategies.
Finally, factors that drive differential disease outcomes, outside of the viral surface proteins, will be assessed in WP3. Here, novel systems will be developed to assess viral infectivity and host range which in turn will enhance our understanding of virus-host interactions and define the role of internal viral proteins, critical to viral replication, driving virus diversity and emergence with consequent disease outcomes. WP3 will utilise outputs from WP1 and WP2 to examine the mechanisms that drive the emergence of virus variants, enabling differential adaptation to different hosts. Experimental systems that enable individual components of the viral replicative machinery to be assessed and compared will be developed, utilising our ability to generate viruses in the laboratory to defined genetic specification. Minimal infectious doses and related growth kinetics will be assessed to refine work in animal models. Utilising expertise from across the UK in different experimental systems, with access to a range of laboratory facilities, the partners will link across WPs to generate impactful outputs to enhance our understanding of these emerging pathogens.
Technical Summary
The UK poultry industry is experiencing severe socio-economic damage and threats from high pathogenicity avian influenza viruses (HPAIVs) H5Nx of clade 2.3.4.4. These viruses pose zoonotic infections risks. The rapid evolution of these viruses is modulating their biological behaviour (epidemiology, host-range, transmission, and pathogenesis) in different avian species. To determine potential risks and improve controls against these emerging and re-emerging viruses requires a comprehensive knowledge base about the nature of prevailing viruses, and an integrated cross-disciplinary approach to studying virus ecology and epidemiology based on understanding virus/host interactions, and the genetic determinants of virulence, transmissibility and antigenicity in wild birds/poultry.
This project will investigate how contemporary H5Nx HPAIVs acquire adaptive changes to increase fitness within domestic and wild avian populations. We will define viral and host factors that potentially contribute to increased transmissibility, persistence, and pathogenicity in wild birds and those that enhance their potential to disseminate and manifest disease in poultry. Evolutionary changes drive virological, immunological and zoonotic infection potential of these viruses therefore, our understanding of environmental and molecular correlates required or associated with successful evolution, immune escape, dissemination and maintenance of HPAIVs via migratory populations of wild birds will be developed. Furthermore, we will define molecular markers for successful interspecies transmission and fitness in poultry with severe clinical outcomes. The will provide insights for assessing threats from new and emerging strains, enabling national and international agencies to design and execute contingencies as part of risk mitigation and disease control. This will provide vital information when considering how to invest scarce resources for surveillance design aimed at early warning of the threat.
This project will investigate how contemporary H5Nx HPAIVs acquire adaptive changes to increase fitness within domestic and wild avian populations. We will define viral and host factors that potentially contribute to increased transmissibility, persistence, and pathogenicity in wild birds and those that enhance their potential to disseminate and manifest disease in poultry. Evolutionary changes drive virological, immunological and zoonotic infection potential of these viruses therefore, our understanding of environmental and molecular correlates required or associated with successful evolution, immune escape, dissemination and maintenance of HPAIVs via migratory populations of wild birds will be developed. Furthermore, we will define molecular markers for successful interspecies transmission and fitness in poultry with severe clinical outcomes. The will provide insights for assessing threats from new and emerging strains, enabling national and international agencies to design and execute contingencies as part of risk mitigation and disease control. This will provide vital information when considering how to invest scarce resources for surveillance design aimed at early warning of the threat.
Publications
Chang P
(2023)
Characterization of the haemagglutinin properties of the H5N1 avian influenza virus that caused human infections in Cambodia.
in Emerging microbes & infections
Furness RW
(2023)
Environmental Samples Test Negative for Avian Influenza Virus H5N1 Four Months after Mass Mortality at A Seabird Colony.
in Pathogens (Basel, Switzerland)
James J
(2023)
Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) from the 2021/22 epizootic is highly duck adapted and poorly adapted to chickens.
in The Journal of general virology
Warren CJ
(2024)
Assessment of Survival Kinetics for Emergent Highly Pathogenic Clade 2.3.4.4 H5Nx Avian Influenza Viruses.
in Viruses
Yang J
(2023)
Novel Avian Influenza Virus (H5N1) Clade 2.3.4.4b Reassortants in Migratory Birds, China.
in Emerging infectious diseases
| Description | 1. Outputs have demonstrated that HP and LP AIV can be detected reliably in small samples of immigrant ducks and geese shot at three discrete locations (see Healthy birds for initial results). HPAIV was detected throughout the core shooting season (October to January), consistent with symptom-free viral excretion by some species. These species are the focus of follow up work in FluTrailMap. This work validates utility of surveillance in these populations for early warning of virus spread to UK and is being built into UK programmes. 2. Collecting and processing faecal samples provides a way of sampling recently deposited virus and obtaining viral sequences from wild birds without having to trap, shoot or net them, and can reveal insights into the 'pre-cursor' and current circulating wild reservoir strains. However, limitations exist in being able to define viral genetic composition from these samples as only fragments were recovered. These approaches to viral detection are being further investigated in FluTrailMap. 3. Using wild bird abundances from eBird (a public citizen science database), spatial associations between wild bird abundances and infected poultry premises per species or species groups and epidemic period were assessed. Species groups such as wildfowl/gulls that have been proposed to play a key role in the epidemiology of HPAIV infection were implicated here, and there was a limited consistent associative role across passerines, near-passerines, or birds of prey. Additionally non-native gamebirds were significantly associated with infected poultry premises during the epidemic period that included main time of release. This vastly adds to knowledge regarding those wild species that present risk for carry virus and inform mitigations designed to keep specified species of wild birds away from domestic poultry. 4. During the HPAIV outbreak period since 2022, GB has experienced the introduction of a range of different H5Nx HPAIVs. From a seasonal perspective, this includes 'autumn' reassortants from migrating birds, and 'spring / over-summering' reassortants, which since the summer of 2021 have been associated with transmission involving seabirds and gulls. These reassortants have been circulating in different but overlapping wild populations, and it is likely that further reassortment will occur. This work has highlighted the need for rapid accessibility of sequences from outbreak events and helps understand critical pathways for emergence of new influenza viruses. 5. Between farm spread. The current HPAIV H5N1 infections in poultry are most likely caused by virus incursions from wild birds rather than via farm-to-farm spread and indicate the importance of strict on farm hygiene/biosecurity measures. Some of this work has helped to inform the recommendations for improved network and wild bird surveillance data that were made in the independent scientific report commissioned by Defra. The UK through APHA have also amended their sampling algorithm from wild birds to try and maximise the opportunity to recover full genetic data from positive birds by taking brain swabs alongside standard swabs. 6. Active sampling on infected premises across different hosts was performed, and the potential role of airborne spread of virus was evaluated. This work, supported by experimental evaluation of pathogenesis and transmission (in WP3 of this project), demonstrated that this virus is not spread long distances by the aerosol route. Important information for the farming community so they focus on addressing other routes where virus enters their farm and informs better protection of farms. Demonstration that virus was unlikely to travel more than a few meters on the air has a significant impact on understanding risk and potential for lateral spread of virus between premises. This gave reassurance to stakeholders across industry with respect to the spread of disease and quelled concerns regarding high-risk activities such as culling and disposal of infected carcasses. 7. Ethnographic observations and qualitative interviews were conducted to understand farmers' perceptions of farm biosecurity and the most common measures being adopted. The study found that poor quality and maintenance of sheds, lack of fencing and gates and poor wild bird biosecurity across many farms appeared to be some of the most common areas requiring improvement. It also revealed that biosecurity measures and their use appeared to be influenced by factors such as cost, education, training and the relationships between stakeholders implementing changes at farm level. Findings also showed the negative impact of AI on the mental health of many individuals in the poultry industry. The study highlighted the need for an improved understanding of key biosecurity risk points and the implementation of effective biosecurity practices, alongside targeted support services and guidance for farmers. The ethnographic outputs showed the strongest and weakest elements of biosecurity on poultry farms, whilst also reflecting on some of the potential barriers to effective biosecurity use. Targeted farm worker education and training could help mitigate against future incursions, while further information on the socio-structural factors impacting the use of biosecurity could help better understand the barriers in implementation. These outputs have defined key recommendations to provide improved avenues for farmers to access educational and training materials including providing training (across different languages) and educational sessions through people with experiences of an AI outbreak. Additionally, further guidance and support services for farmers and others in the industry could help prevent and limit the negative impacts AI has had on mental health, while further quantitative and qualitative research will help us understand more about the topic in detail. Such areas will be investigated in Flutrailmap. 8. Stakeholder / policy mapping and user case studies to support risk management and communication.Interview outputs included areas for improvement in avian influenza outbreak stakeholder collaboration, communication, and risk mitigation measures. These are communicated in a policy brief to be shared with the UK Chief Veterinary Officer. Furthermore, feedback regarding the user experience of the GOV.UK avian influenza webpage has been relayed back to communications to amend the website. 9.We assessed the emergence of genetically related viruses over time enabling the development of tools to explore differences in the composition of viral glycoproteins and the impact of antibodies directed against them. These tools were developed to help understand the role of antibodies to surface proteins and by extension, the role of prior immunity in the emergence of viruses. Further assessment was tailored to evaluate whether key antigenic regions can be targeted to enable cross reactive antibody responses. Through investigation of serological reactivity to contemporary H5Nx viruses, we have started to assess how viruses emerge in the face of significant prior exposure to cause infection across a broad range of Anseriforme species. Understanding the impact and long-term effect of HPAIV and indeed AIV circulation in wild birds helps us in being able to indicators where further impacts on bird populations may occur and drivers influencing potential survival from the ongoing circulation of HPAIV. The tools developed as part of FluMAP are being deployed in FluTrailMap to define the circulation and role of antibodies in different wild bird populations. 10. Understanding where molecular evolution may be driven through antigenic pressures (via host responses to infection) is critical to understanding how viruses may emerge following virus incursion into populations of vaccinated birds. The work undertaken in FluMAP has signalled that these viruses are able to undergo genetic changes that may enable them to escape vaccination and this work has established a background of viral variants that will be analysed further in FluTrailMap. This work puts down key markers to consider when thinking of vaccination in the future. 11. The initial emergence of H5Nx viruses, against a background of H5N8 dominance in the UK and Europe during 2020-2021, and the subsequent emergence of H5N1 as a virus that has gone on to dominate globally led to the need to interrogate virus protein interactions. Assays were developed to investigate the interaction and stability of interactions between different virus protein combinations. what made the H5N1 viruses successful and fit? This demonstrated that the evolution of the virus from H5Nx to a dominant H5N1 as being more stable and therefore a critical factor behind the emergence of the H5N1 subtype as a stable surface protein pairing that has then spread globally to cause a devastating panzootic. The development of this assay has also enabled future assessment of surface protein combinations which may enable greater viral stability. It will enable rapid prediction of risk carried by new strains as they emerge. 12. To define non-antigenic viral factors that contribute to pathogenicity and disease emergence. Alongside understanding the impact of different glycoprotein (virus proteins) combinations on the surface of the virus, bespoke viruses were developed to enable an assessment of the role of internal genes on the outcome of infection. Throughout the panzootic, a number of reassortment events led to the emergence of a number of distinct genotypes within the H5N1 subtype. Each of these differed in the composition of internal genes and this task set about to define the roles of different internal gene segments in virus survival, infection dynamics and replicative efficiency in different systems. Definition of the different genotypes present in the UK is critical to tracking viral reassortment and risk (FLUMAP:Genetics). Further, understanding the impact of genotypic changes on disease outcome is critical to understanding these viruses. Virulence for poultry was evaluated with an early genotype that dominate during the 2021-22 season. Experimental evaluation of pathogenesis and transmission for the AIV-07-B2 genotype (FLUMAP: Pathogenesis) showed that ducks shed large amounts of infectious material whilst chickens, in contrast, shed comparatively little infectious material. Later experimentation with AIV-09 and AIV-48 (Manuscript in preparation) has demonstrated differences in infection dynamics and transmission profiles. Replication dynamics of low pathogenic avian influenza viruses and a high pathogenic avian influenza virus were also compared across duck and chicken cell lines to develop a rapid assay for screening emerging avian influenza viruses for replication fitness and pathogenic potential. Identifying viral factors that dictate the emergence and long-term stability of different subtypes is critical to understanding the threat from these viruses. Pathogenesis studies have reflected field observations and have enabled a stronger understanding of different shedding profiles and hence the infectivity of different genotypes. A rapid standardised assay evaluating virus replication across avian species can be used to rank emerging viruses. 13. Understanding the genetic markers of H5 HPAIV fitness. Panels of H5 viruses were generated using a technique called reverse genetics techniques to facilitate the study of individual molecular markers of virulence. The detection of H5Nx viruses containing different combinations of the NA gene led to an investigation of the relationships between two external viral glycoproteins HA and NA. How these two different viral coat proteins interact with each other and what optimal protein combinations mean with respect to stability of interaction demonstrated that H5 and N1 had likely emerged as a consequence of the interactions between these two proteins with other pairings, such as H5N8, also demonstrating greater protein: protein stability than other potential pairings. Using bioinformatics approaches and functional characterisation we identified the T156A polymorphism (mutation switch) in the HA as potentially a key marker for H5N8 to H5N1 shift. This 156A mutation has emerged in H5N1 viruses over the epizootic period, correlating with the expansion of H5N1 and shows higher fitness with N1 NA, and low fitness with N8 NA. Through analysis of the replication of these viruses in ex vivo trachea organ cultures (to mimic what happens in the bird) revealed a rapid loss of tracheal ciliary activity and infection pathology. The severity of this was mapped to internal gene segments of H5N1, providing insight into the gene segments required for infection pathology. How efficient each different viral gene (polymerase complex) was at replicating the viral genetic material was also investigated. The polymerase activity of H5N8 (2020) is weaker compared to H5N1 (current epizootic). This weaker polymerase activity of the H5N8 virus from 2020 relative to H5N1 maps to two genes, the PB2 and PA segments, suggesting the fitness of H5N1s is (at least partially) due to acquisition of novel polymerase genes. We also investigated the role of other viral internal gene segments. Studies within the project have demonstrated that H5N1 viruses have an enhanced ability to switch off host innate responses by the NS1 viral gene but not by PA-X gene compared with H5N8. These findings through in vitro assessments have demonstrated a virological basis for the success of the H5N1 subtype through optimal glycoprotein and internal gene interactions. Allowing us to better appreciate the factors affecting pathogenesis, virulence and disease outcomes for the current H5N1 and future potential threats from AIV. 14. Understanding the changes to H5N1 genetics which enable the virus to newly spread to mammals. Evaluating the presence of mutations associated with mammalian adaptation both in vitro (in the lab) and in vivo (in the live ??) has demonstrated the criticality of small mutation events within key genes on the replicative ability of these viruses. We evaluated the way the virus attaches to its target host cell through what are known as viral receptors. The binding preference for H5N1 HPAIVs, demonstrating a strong presence of these viruses to bind receptors found on avian cells, albeit with variable binding kinetics. However, these viruses exhibit limited binding to receptors typically found on human cells . Furthermore, studies have demonstrated that these viruses optimally replicate at a pH consistent with avian, rather than mammalian influenza viruses, indicating the H5N1 viruses have reduced potential for mammal-to mammal, and by extension, human-human transmission. The effect of mutations that have been detected in these viruses following infection in mink and domestic cats was also investigated, demonstrating that these mutations can boost polymerase activity in human cells ie direct the host cell to produce more virus. This work has demonstrated that the internal gene changes that occur following coinfection and reassortment can have differential effects in avian versus human systems. These analyses provide greater granularity around the risk of the current H5N1 HPAIVs to human health. Viruses and mutations generated during this study will be utilised to further investigate these factors as part of FluTrailMap a follow on linked grant. |
| Exploitation Route | The scientific progress made in this grant has been substantial and directly feeds a follow on grant called flutrailmap (same UK consortia of research organisations) that will directly build on the progress made and utilise assays and reagents developed in this project. The published outputs will be used by the influenza research community (including internationally) and applied to address related questions regarding drivers of pathogen emergence and infection outcome including host range. Further the consortia working on this grant has freely shared materials developed in the project with the UK research community. In particular this has included key UKHSA laboratories addressing pandemic preparedness and response which has been accelerated since the project finished owing to the spill over of this bird virus to dairy cattle in the USA ringing alarm bells for public health scientists should the virus make the further jump to humans. This would increase use of the tools and reagents from this grant yet further. Fundamental science underpinning vaccination will have relevance to the private sector looking to exploit vaccine technologies. The close engagement with the commercial poultry industry will over time inform improved practices for farm hygiene (to reduce risk of spread of disease) and these will be introduced and implemented by the sector. Further government officials concerned with planning execution and engagement with industry over outbreak preparedness and response have markers for improvement identified in this project. |
| Sectors | Agriculture Food and Drink Environment Government Democracy and Justice |
| Description | Improved practices in industry to improve farm hygiene have contributed to a sharp reduction in the number of disease outbreaks. In period 2022-23 there were over 360 UK outbreaks, in q4 2023 to 2024 there have only been 5. Multiple factors will underly so source attribution not possible to define. This major reduction in numbers of birds affected by this severe disease has led to much benefit for improved animal health and welfare. Reduced negative environmental impact and release of virus that can affect wild populations; mammals and birds. Cases in wild birds and mammals have sharply declined. Economic impact; lack of outbreaks means the UK has been able to declare disease freedom with the ability to reopen global trading markets (multi billion industry) that become blocked during periods of disease outbreaks. The estimated cost of the 2022-23 outbreak was 100 million. Again attribution multiple factors and not possible to define. Public health benefit; the knowledge gained in this project has informed assessments on the risk to public health from these viruses which then trigger preparedness levels lead by DHSC/UKHSA thereby ensuring human health is protected. For example a tender has been issued for a small emergency stock of pre-pandemic H5 vaccine to ensure quality of life and human health is protected should human transmissibility be acquired by these avian viruses. Science evidence from the project has informed multiple animal disease risk assessments which have directly shaped and changed animal disease control policy (Defra and Devolved Administrations of the UK) another tenet of successful control and prevention. Again multiple factors will underly so source attribution not possible to define. International impact impossible to define but some of the fundamental knowledge gains have been used by others in shaping policy for improved disease control and mitigation performance. Evidenced by outputs being referenced in 230 policy documents from 59 sources/14 countries/4 continents. Note not all these can be attributed directly to the grant as the search engine does not facilitate but it does give an indication of global reach. Academic; we anticipate these systems and approaches will be used by others to research ongoing risk from influenza viruses. Citation indices when all publications have matured will be informative. Impact will be further assessed annually including through the flutrailmap follow on programme. |
| First Year Of Impact | 2023 |
| Sector | Agriculture, Food and Drink,Environment,Government, Democracy and Justice |
| Impact Types | Societal Economic Policy & public services |
| Description | Animal Disease Policy Group |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Data from animal disease surveillance directly informed risk levels for incursion of avian influenza to kept birds in the UK. The advice provided gave an evidence base to invoke specific disease mitigation measures to include the imposition of disease prevention zones and housing orders for domestic poultry. |
| Description | Defra Science Advisory Council |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Decisions on application of measures to control HPAI. Their reach to different parts of society. Implementation and release of poultry housing orders. Direction to start planning for vaccination as a contingency. Issuing new guidelines to industry to improve biosecurity practices with evidence (from grant) as to how failures were occurring. As the outbreak evolved across 2021-2024 so did better implementation of biosecurity in the poultry sector reducing disease risk/burden and lower cases eased pressures on the public purse. |
| URL | https://www.gov.uk/guidance/bird-flu-avian-influenza-how-to-prevent-it-and-stop-it-spreading |
| Description | NERVTAG |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Provision of scientific risk assessment and mitigation advice on the threat posed by new and emerging respiratory viruses and on options for their management. My involvement contributed to discussions, decisions and recommendations made by NERVTAG to the UK Government. |
| URL | https://www.gov.uk/government/groups/new-and-emerging-respiratory-virus-threats-advisory-group |
| Description | OFFLU |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | OFFLU data is used by national governments to build appropriate science capacity and follow approaches to control animal influenzas. The reach extends to protecting public health through provision of science data to WHO who apply in their pandemic preparedness work for tracking risk and vaccine intervention. |
| URL | https://www.offlu.org/index.php/4437-2/ |
| Description | Seminar hosted at British Embassy during WOAH general session |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
| Description | TARZET |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| Impact | Risk levels impact public health triggers for disease prevention/pandemic preparedness. Continuous and ongoing review through this group. Data from the project is presented at each meeting and is fundamentally used in reviewing risk from H5 HPAI. Flutrailmap (project acronym) is widely acknowledged in TARZET outputs including those in public domain. In particular high frequency of review since 2024 due to spread of virus to dairy cattle and increasing numbers of human cases, which also necessitated need to fully understand viruses in reservoir hosts ie birds to influence decision making on risk levels. |
| URL | https://assets.publishing.service.gov.uk/media/66a0ff6dfc8e12ac3edb03e4/AH5N1-risk-assessment-july-2... |
| Description | UK vaccination working group on Avian Influenza |
| Geographic Reach | Europe |
| Policy Influence Type | Contribution to a national consultation/review |
| Impact | Knowledge of how the virus is changing and utility of vaccination directly shaped thinking in UK and beyond. The PI gave several presentations to European stakeholders on the emerging science and what it meant. This information was received by national governments some of whom accelerated preparedness plans to develop vaccination contingency plans. Importantly several updates on vaccines their development, trials, use and application were given to working group members (up to 2025 group still active). Data derived from the project helped set context for these presentations. |
| Title | Airborne sampling for virus particles on farm |
| Description | Validation of air samplers and their siting on infected farms/regions near to track airborne dispersal |
| Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | The method resulted in strong evidence refuting airborne spread of HPAI between poultry premises. This had important implications for industry operatives to concentrate on other aspects of farm biosecurity to reduce risk of incursion |
| URL | https://www.mdpi.com/1999-4915/15/4/1002 |
| Title | Cohousing of poultry species to investigate cross species transmission of HPAI |
| Description | The model was evaluated in an experimental setting to track and monitor if viruses can spread between different poultry hosts and modes of transmission/disease outcomes. |
| Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | These models were worked up and applied to ongoing disease events in the field. Findings were correlated with field observations and evidence used to inform future early warning/monitoring for disease and assessing risk to different populations |
| Title | Functional assays to measure role of different virus proteins |
| Description | Scaled ability to produce reverse engineered viruses from genomic sequences and then define phenotype in functional assays measuring host receptor binding/specificity and pH of fusion for endocytosis. These are critical parameters to track/predict for changes in risk in emerging influenza A viruses. We have established a fast track efficient system applied to 10's of strains in months. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| Impact | We have been able to screen emerging variants of avian and cattle H5 HPAI viruses which are fast evolving. The system has enabled a pipeline of viruses to be generated from genomic data (thereby avoiding need for shipment of biologicals and hence reducing time to respond) during a fast moving disease event in Europe and North America. The data has been instrumental in informing ongoing national and international risk assessments that in turn shape preparedness and response plans. ie UK took decision in late 2024 to procure supplies of H5 pre pandemic vaccine. This tool enables data that feeds larger assessments. |
| Title | Functional assays to measure role of different virus proteins |
| Description | development and validation of a reverse genetics system to study the role of individual genes/amino acid markers for biological traits |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | The consortia were able to effectively establish the genetic traits underlying rapid global spread of a strain of high pathogenicity avian influenza. This information was used to inform national risk assessments in the one health arena. |
| Title | Research questionnaire/approaches to assess farm biosecurity |
| Description | Development of a tool in partnership with the poultry industry that was then used to interview a range of industry operatives in order to identify factors that impact application and effectiveness of farm biosecurity methods |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | A report to industry on factors influencing good farm biosecurity has been shared and the findings have been submitted for peer review publication. Senior industry leaders are considering how the findings can be developed into best practice |
| Title | Toolbox for dissecting immune responses to infection with multiple influenza A sutbtypes |
| Description | Using pseudotype antigen's we built a library to all serotypes of the HA and NA proteins of influenza A viruses |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | Impacts early but enable dissection of wild bird immune responses to H5 or other flu subtypes. This will transform our understanding of population susceptibility and enable dissection of evolutionary drivers for emergence of new strains. It also has a large positive impact for biosafety and costs since these assays do not use live virus and can been done outside specialist high containment antibody facilities |
| Title | Biobank of samples collected from a range of poultry hosts infected with different strains of avian influenza |
| Description | Experimental infections of birds in secure biocontainment facilities have resulted in a large biobank of samples being collected that are available for future analytical work |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | The materials harvested and stored are available to two follow on research consortia with new grants post completion of flumap. This will increase scope of analysis and apply reduction to use of animals. The biobank is being used and added to by experimentally generated materials in flutrailmap. |
| Title | Database of UK farms associated with HPAI outbreaks |
| Description | List of premises suffering outbreaks to allow enhanced epidemiological analyses and to build network of farm connectivity |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | To use as a tool for future disease modelling and measuring impact of interventions. To date these models have enable dissection of the drivers behind farm infection. Some associations with wild bird demographic that will be developed further in the follow on grant flutrailmap. |
| Description | OFFLU network |
| Organisation | Food and Agricultural Organisation (FAO) |
| Country | Italy |
| Sector | Charity/Non Profit |
| PI Contribution | We have shared disease intelligence and latest research findings relating to the evolution of avian influenza viruses. This includes how genomic changes are impacting the antigenic characteristics of the virus which in turn shapes outputs informing vaccine strain selection and appropriate diagnostics.Genomic intelligence also underpins international nomenclature and naming of influenza viruses. It has contributed to OFFLU position documents used globally to inform disease risk, preparedness and interventions. |
| Collaborator Contribution | OFFLU is an open international network of expertise on animal influenza and provides access to a large number of institutes and organisations researching avian influenza. This has given the project privy access to virus genomic data and disease epidemiology not in the public domain. Access to confidential datasets relating to vaccine matching for both animal and human interventions. |
| Impact | Data and intelligence shared has shaped and been used to inform international vaccine strain selection for human pandemic preparedness. These considerations under the auspices of WHO are held twice a year. https://www.offlu.org/wp-content/uploads/2025/03/OFFLU-vcm-avian-2025a-Final.pdf |
| Start Year | 2010 |
| Description | The Crick Institute |
| Organisation | Francis Crick Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Provision of avian influenza expertise and intellectual input. Collaborative research and networking. Broader perspectives on One Health issues as it relates to the programme. |
| Collaborator Contribution | Collaborative research and networking. |
| Impact | Collaborative research and networking. |
| Start Year | 2023 |
| Description | AgriLand online article - NFU welcomes new taskforce to tackle avian influenza |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Online article in AgriLand highlighting the NFU's support for the FluMAP project |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.agriland.co.uk/farming-news/nfu-welcomes-new-taskforce-to-tackle-avian-influenza/ |
| Description | BBC Radio 4 - Farming Today - Bird Flu Consortium Launched |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Radio interview with Ian Brown on the launch of the FluMAP consortium. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.bbc.co.uk/programmes/m0018ftk |
| Description | BBC article - H5N1: UK taskforce set up to tackle bird flu spread |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | BBC article on their website announcing that the FluMAP project had been funded and was underway. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.bbc.co.uk/news/science-environment-61818790 |
| Description | Courier Evening Telegraph - Top scientists join forces to battle bird flu |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Courier online article explaining £1.5 million of funding for a new research consortium composed of some of the UK's top scientists. Includes quotes from CVO-UK and UKRI. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.thecourier.co.uk/fp/business-environment/farming/3413535/top-scientists-join-forces-to-b... |
| Description | Daily Mail article - How fowl! Bird flu rise is blamed on trend for keeping chickens in gardens as UK taskforce is allocated £1.5 million to tackle the spread |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Daily Mail newspaper and online article highlighting bird flu and the new Government funding to research it as part of the FluMAP project. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.dailymail.co.uk/sciencetech/article-10933047/How-fowl-Bird-flu-rise-blamed-trend-keeping... |
| Description | East Anglian Daily Times - New research project aims to curb Suffolk's nine bird flu outbreaks |
| 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 | Online article on new research project that will study bird flu outbreaks, including nine from Suffolk earlier this year, to help understand how the influenza is evolving. The one-year project has been named 'FluMap' and aims to combat the latest strain of highly pathogenic avian influenza (H5N1) in the United Kingdom. Highlights project but without mentioning consortium member organisations. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.eadt.co.uk/news/21258856.new-research-project-aims-curb-suffolks-nine-bird-flu-outbreaks... |
| Description | EuroWeekly News online article - UK's top scientists join forces to battle bird flu outbreaks |
| 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 | News article published as a result of initial press release about FluMAP. Eight of the UK's top scientific organisations coming together to find new ways to contain bird flu outbreaks the UK government have announced today, June 20. The eight-strong consortium, headed by the world-leading research team at the Animal and Plant Health Agency (APHA), has received £1.5 million from the Biotechnology and Biosciences Research Council (BBSRC) and the Department for Environment, Food and Rural Affairs (Defra) and has been tasked with developing new strategies to tackle future bird flu outbreaks. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://euroweeklynews.com/2022/06/20/uks-top-scientists-join-forces-to-battle-bird-flu-outbreaks/ |
| Description | Farmer's Weekly magazine - Scientists join forces to tackle avian influenza outbreaks |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Article in Farmer's Weekly magazine and online highlighting new FluMAP research project. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.fwi.co.uk/livestock/health-welfare/scientists-join-forces-to-tackle-avian-influenza-outb... |
| Description | Farmers Guardian article - Scientists join forces to fight avian flu crisis |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Farmers Guardian article highlight new project and need for biosecurity in relation to avian influenza. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.fginsight.com/news/scientists-join-forces-to-fight-avian-flu-crisis-128659 |
| Description | Global poultry industry |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Ad-hoc advice and numerous visits to third countries. Some advice provided to policy makers formulating control policy against AI. Data/knowledge gained form research contributed to personal CPD and expertise therein. Keynote speaker International meeting hosted by IABS on Overcoming barriers to avian influenza vaccination'. |
| Year(s) Of Engagement Activity | 2011,2012,2013,2014,2015,2016,2017,2018,2023,2024 |
| Description | Gov.UK Blog - APHA, Defra and BBSRC have today announced a major new research consortium in the UK's battle against bird flu. |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | APHA Science Blog posted on the Government Science & Engineering Profession blog page explaining about the new consortium of FluMAP. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://governmentscienceandengineering.blog.gov.uk/2022/06/20/apha-defra-and-bbsrc-have-today-annou... |
| Description | Guardian article - Bird flu is on the rise in the UK. Are chickens in the back garden to blame? |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Guardian newspaper and online article featuring interview with Ian Brown, highlighting FluMAP as a newly funded research project. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.theguardian.com/world/2022/jun/19/bird-flu-rise-are-chickens-in-back-garden-to-blame |
| Description | Guardian article - UK vulnerable to major animal disease outbreaks, report finds |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Guardian article on APHA's facilities in light of the PAC report highlighting the need for development of site. Features quote from James Wood, consortium partner and member of APHA's Science Advisory Board. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.theguardian.com/science/2022/nov/16/uk-vulnerable-to-major-animal-disease-outbreaks-repo... |
| Description | International symposia on AI |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Ian Brown co-chaired this major international event presenting the latest science on AI; ongoing commitment to this fora |
| Year(s) Of Engagement Activity | 2012,2015,2018,2023,2024 |
| URL | http://www.flu-lab-net.eu |
| Description | Mirage News online - Scientists help to battle bird flu outbreaks in UK |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Mirage News article online highlighting new funding for FluMAP and involvement of University of Nottingham. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.miragenews.com/scientists-help-to-battle-bird-flu-outbreaks-in-804010/ |
| Description | New Scientist article - UK bird flu research project launched to protect poultry and seabirds |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | New Scientist article featuring a UK government-backed project - FluMap - aims to help understand how bird flu is evolving and finding its way into poultry farms. Includes interview quotes with Ian Brown. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://institutions.newscientist.com/article/2325036-uk-bird-flu-research-project-launched-to-prote... |
| Description | Poultry industry |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Provision of science evidence from AI research to stakeholder groups in the UK poultry industry. Data used by industry to make business decisions related to AI threat. Addressing UK core group of poultry experts drawn from across industry. |
| Year(s) Of Engagement Activity | 2010,2011,2012,2013,2014,2015,2016,2017,2018,2023,2024 |
| Description | Press Release UK's top scientists join forces to battle bird flu outbreaks |
| 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 | Media (as a channel to the public) |
| Results and Impact | Published on gov.uk to highlight UKRI funding for FluMAP project. Resulted in wide media interest from a variety of sources. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.gov.uk/government/news/uks-top-scientists-join-forces-to-battle-bird-flu-outbreaks |
| Description | Public engagement via media interviews |
| 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 | A series of media interviews both TV and online newspapers to understand current risks to the public from H5 avian influenza. Increase in requests consequent with spread of virus to cattle in the USA. Support to UK science media centre to provide impartial comment on utility and importance of public release of new major research findings in my field using knowledge of emerging research in this project. |
| Year(s) Of Engagement Activity | 2023,2024,2025 |
| Description | RVC joins UK's top scientists to combat increasing cases of bird flu |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | RVC website article highlighting their involvement in the FluMAP consortium |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.rvc.ac.uk/research/news/general/rvc-joins-uk-s-top-scientists-to-combat-increasing-cases... |
| Description | Sky News YouTube interview - Experts warn bird flu has slipped 'through our fingers' |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | YouTube video from Sky News featuring Ian Brown interview, RSPB interview and footage of wild birds and lab activities at APHA. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.youtube.com/watch?app=desktop&v=HIKwAInaftA |
| Description | Uk research fora |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | wide range of fora where UK researchers formally come together via events/meetings to exchange scientific research knowledge |
| Year(s) Of Engagement Activity | 2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018,2023,2024 |
| Description | Vet Times article - Scientists join forces in major offensive against bird flu |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Article on new FluMAP project for Vets. Includes interview quotes from APHA, RVC and Pirbright. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.vettimes.co.uk/news/scientists-join-forces-in-major-offensive-against-bird-flu/ |
| Description | Website article - Government provides funding for avian influenza research |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Article by the National Farmers Union highlighting the funding provided for the FluMAP project. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.nfuonline.com/updates-and-information/government-provides-funding-for-avian-influenza-re... |
| Description | Website article - Leeds expert joins Government bird flu task force |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | Website article highlighting involvement of Dr Alastair Ward with FluMAP consortium. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.leeds.ac.uk/news-science/news/article/5108/leeds-expert-joins-government-bird-flu-task-f... |