Accelerated development of a safe and easily manufactured Q fever vaccine
Lead Research Organisation:
Moredun Research Institute
Department Name: Disease Control
Abstract
Q fever is an important and highly contagious disease of worldwide importance affecting both livestock and humans caused by the intracellular Gram-negative bacterium, Coxiella burnetii. Infection of humans occurs following exposure to as few as 1-10 bacteria and can result in both acute and chronic forms of disease. Infections can result in death, especially in the elderly or immunocompromised. Livestock, in particular sheep and goats, are the major source of human infections where infection can cause abortion, stillbirth and delivery of weak offspring. The loss of lambs and kids can result in devastating economic losses to the livelihoods of farmers in Europe as well as LMIC countries, particularly during abortion storms where up to 35% losses can occur.
Vaccines are currently considered the most effective way to control Q fever, and vaccines based on inactivated C. burnetii organisms are commercially available for use in both ruminants and humans. However, the safety of these vaccines is a major issue considering that severe local and systemic reactions occur post-vaccination in humans previously exposed to the bacteria and vaccination of ruminants is associated with significant production losses. Furthermore, manufacture of these vaccines involves culture of the organisms, which has both cost and safety issues. These issues have resulted in limited use of these vaccines. There is therefore an urgent need to develop safe, effective and easily manufactured vaccines to control Q fever in both humans and livestock species.
To this end, attempts have been made to develop subunit vaccines targeting key C. burnettii proteins which would be safer to manufacture and could be engineered to induce fewer side effects following vaccination. However, current approaches to subunit vaccine development have been severely hampered by a lack of knowledge of the appropriate bacterial proteins to target.
In this project, we will use novel peptide chip array technology to identify the key C. burnetii proteins recognised by antibodies from sheep and goats vaccinated with the current protective, but unsafe commercial vaccine in a high throughput and detailed manner. These antibody responses will be compared with those generated by a non-protective C. burnetii vaccine which is based on a different (non-virulent) form of the bacteria. By comparing antibody responses from protected and non-protective vaccines, bacterial proteins which are specifically targeted by the protective vaccine will be identified. Synthetic versions of these proteins will then be generated and subunit vaccines based on pools of these proteins will be tested in a sheep challenge model. This will provide preliminary safety and efficacy data to inform future Q fever vaccine development programmes.
Vaccines are currently considered the most effective way to control Q fever, and vaccines based on inactivated C. burnetii organisms are commercially available for use in both ruminants and humans. However, the safety of these vaccines is a major issue considering that severe local and systemic reactions occur post-vaccination in humans previously exposed to the bacteria and vaccination of ruminants is associated with significant production losses. Furthermore, manufacture of these vaccines involves culture of the organisms, which has both cost and safety issues. These issues have resulted in limited use of these vaccines. There is therefore an urgent need to develop safe, effective and easily manufactured vaccines to control Q fever in both humans and livestock species.
To this end, attempts have been made to develop subunit vaccines targeting key C. burnettii proteins which would be safer to manufacture and could be engineered to induce fewer side effects following vaccination. However, current approaches to subunit vaccine development have been severely hampered by a lack of knowledge of the appropriate bacterial proteins to target.
In this project, we will use novel peptide chip array technology to identify the key C. burnetii proteins recognised by antibodies from sheep and goats vaccinated with the current protective, but unsafe commercial vaccine in a high throughput and detailed manner. These antibody responses will be compared with those generated by a non-protective C. burnetii vaccine which is based on a different (non-virulent) form of the bacteria. By comparing antibody responses from protected and non-protective vaccines, bacterial proteins which are specifically targeted by the protective vaccine will be identified. Synthetic versions of these proteins will then be generated and subunit vaccines based on pools of these proteins will be tested in a sheep challenge model. This will provide preliminary safety and efficacy data to inform future Q fever vaccine development programmes.
Technical Summary
Q fever vaccines based on formalin inactivated phase I C. burnetii are protective but have considerable safety issues, both in terms of their manufacture and post-vaccination reactions. Vaccines based on the avirulent inactivated phase II C. burnetti are safer but non-protective. The aim of this project is to identify C. burnetii protein antigens which contribute to the protection induced by the phase I vaccine in order to rationally design a safe subunit Q fever vaccine.
To do this we will use novel high-density peptide chip arrays representing all open reading frames of the C. burnetii vaccine strain (strain RSA493) in 15-mer overlapping peptides. Pooled serum from sheep and goats vaccinated with the phase I vaccine will be used to probe peptide chips to identify antibody reactive peptides. Positive peptide hits from pooled serum samples will be validated at the individual animal level by ELISA using individual peptides. Pooled serum samples from sheep vaccinated with the phase II vaccine as well as samples from sheep, goats and humans exposed to C. burnetii will also be examined to identify peptides which are uniquely recognised by serum from individuals vaccinated with phase I but not phase II vaccines, and those unique to serum from exposed individuals (potential DIVA targets).
Once we have identified a panel of peptides which are associated with the protective vaccine, we will infer the protein target of peptide by comparison with the C. burnetii strain RSA493 genome, and select proteins which are recognised by all phase I vaccinated individuals. Proteins will be further selected based on known importance for C. burnetii virulence-related functions and sequence conservation between C. burnetii strains. The final pool of proteins will be synthesised as E. coli recombinant proteins. Prototype vaccines based on pools of these recombinant proteins will be tested for safety, immunogenicity and efficacy in a pregnant sheep C. burnetii challenge model.
To do this we will use novel high-density peptide chip arrays representing all open reading frames of the C. burnetii vaccine strain (strain RSA493) in 15-mer overlapping peptides. Pooled serum from sheep and goats vaccinated with the phase I vaccine will be used to probe peptide chips to identify antibody reactive peptides. Positive peptide hits from pooled serum samples will be validated at the individual animal level by ELISA using individual peptides. Pooled serum samples from sheep vaccinated with the phase II vaccine as well as samples from sheep, goats and humans exposed to C. burnetii will also be examined to identify peptides which are uniquely recognised by serum from individuals vaccinated with phase I but not phase II vaccines, and those unique to serum from exposed individuals (potential DIVA targets).
Once we have identified a panel of peptides which are associated with the protective vaccine, we will infer the protein target of peptide by comparison with the C. burnetii strain RSA493 genome, and select proteins which are recognised by all phase I vaccinated individuals. Proteins will be further selected based on known importance for C. burnetii virulence-related functions and sequence conservation between C. burnetii strains. The final pool of proteins will be synthesised as E. coli recombinant proteins. Prototype vaccines based on pools of these recombinant proteins will be tested for safety, immunogenicity and efficacy in a pregnant sheep C. burnetii challenge model.
Planned Impact
Who might benefit from this research?
At sequential stages of the project, scientists involved in vaccinology; commercial and non-profit vaccine manufacturers and distributors in developed countries and Low to Middle Income Countries (LMICs); livestock producers and meat industry workers (veterinarians, farmers, stockmen, dairymen, abattoir workers, animal transport workers, animal traders) in developed countries and LMICs worldwide; populations of humans living in close proximity to animals where agriculture and animal husbandry are significant sources of income.
How might they benefit from this research?
Scientists involved in vaccinology will benefit directly from the novel approach to antigen identification and will receive novel information on these processes via our Pathways to Impact, which may have direct downstream impact on their approach to vaccine production for a range of other viral, bacterial and multi-cellular pathogens. Vaccine manufacturers and distributors will benefit by having a safe, effective, easy to manufacture product which is also easy to store and administer. Coxiella burnetii infection in domesticated livestock has been associated with abortions, especially in sheep and goats, and infertility in cattle and therefore can have a profound economic impact on production worldwide[1]. The availability of a novel, cost-effective and protective vaccine for use in animals therefore benefits livestock producers but also helps to protect veterinary and agricultural workers by limiting their exposure to the pathogen, resulting in increased productivity and quality of life [2]. The potential public health benefits of an effective livestock vaccine can be illustrated by the 2007-2010 Q fever epidemic in the south-east Netherlands where >3000 cases of Q fever were notified in that short period. In this scenario, only ~3% of patients worked in the agricultural sector and only 0.5% worked in the meat-processing industry but the geographical area of the epidemic was densely populated and intensively farmed with dairy goats, resulting in the suspected transmission of contaminated dust from Coxiella-infected goats to humans living close-by [3]. Control measures including mandatory vaccination and culling on infected farms brought the epidemic to an end.
References
[1] Stark et al. Schweizer Archiv fur Tierheilkunde 139, 343-353.
[2] Kermode et al., Aust N Zealand J Public Health, 27, 390-398.
[3] Dijkstra et al. Immunol Med Microbiol 64, 3-12.
At sequential stages of the project, scientists involved in vaccinology; commercial and non-profit vaccine manufacturers and distributors in developed countries and Low to Middle Income Countries (LMICs); livestock producers and meat industry workers (veterinarians, farmers, stockmen, dairymen, abattoir workers, animal transport workers, animal traders) in developed countries and LMICs worldwide; populations of humans living in close proximity to animals where agriculture and animal husbandry are significant sources of income.
How might they benefit from this research?
Scientists involved in vaccinology will benefit directly from the novel approach to antigen identification and will receive novel information on these processes via our Pathways to Impact, which may have direct downstream impact on their approach to vaccine production for a range of other viral, bacterial and multi-cellular pathogens. Vaccine manufacturers and distributors will benefit by having a safe, effective, easy to manufacture product which is also easy to store and administer. Coxiella burnetii infection in domesticated livestock has been associated with abortions, especially in sheep and goats, and infertility in cattle and therefore can have a profound economic impact on production worldwide[1]. The availability of a novel, cost-effective and protective vaccine for use in animals therefore benefits livestock producers but also helps to protect veterinary and agricultural workers by limiting their exposure to the pathogen, resulting in increased productivity and quality of life [2]. The potential public health benefits of an effective livestock vaccine can be illustrated by the 2007-2010 Q fever epidemic in the south-east Netherlands where >3000 cases of Q fever were notified in that short period. In this scenario, only ~3% of patients worked in the agricultural sector and only 0.5% worked in the meat-processing industry but the geographical area of the epidemic was densely populated and intensively farmed with dairy goats, resulting in the suspected transmission of contaminated dust from Coxiella-infected goats to humans living close-by [3]. Control measures including mandatory vaccination and culling on infected farms brought the epidemic to an end.
References
[1] Stark et al. Schweizer Archiv fur Tierheilkunde 139, 343-353.
[2] Kermode et al., Aust N Zealand J Public Health, 27, 390-398.
[3] Dijkstra et al. Immunol Med Microbiol 64, 3-12.
Organisations
- Moredun Research Institute (Lead Research Organisation)
- Animal and Plant Health Agency (Collaboration)
- Ceva Sante Animale (Collaboration)
- University of Bern (Collaboration)
- Friedrich Loeffler Institute (Collaboration)
- Slovak Academy of Sciences (Collaboration)
- National Institute for Biological Standards and Control (NIBSC) (Collaboration)
Publications
Bach E
(2023)
Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection.
in Frontiers in immunology
McNeilly TN
(2019)
Q fever: An emerging problem in LMIC and the need for improved vaccines
in Open Access Government
Williams-MacDonald SE
(2023)
Efficacy of Phase I and Phase II Coxiella burnetii Bacterin Vaccines in a Pregnant Ewe Challenge Model
in Vaccines
Williams-Macdonald SE
(2023)
Efficacy of Phase I and Phase II Coxiella burnetii Bacterin Vaccines in a Pregnant Ewe Challenge Model.
in Vaccines
Description | Through this project we have determined that the currently available Q fever vaccine (Coxevac) is protective against challenge with Coxiella burnetii (the causative agent of Q fever) for the first time. Furthermore the vaccine did not induce significant injection site or systemic reactions following vaccination in sheep. This provides supportive evidence that the vaccine, which is currently only licensed for cattle and goats, can be deployed safely in sheep to effectively control Q fever in this species. This information has now been successfully used to extend the European license claim of Coxevac to include use in sheep. We have also revised the genome of the current C.burnetii strain of bacteria which is used in the Coxevac vaccine and have identified an additional 400 potential genes (and therefore proteins) within C. burnetii genome. This allowed us to develop a method (called peptide microarray) to identify the C. burnetii proteins targetted by the vaccine, which may be responsible for its protective effect. This analysis identified ~200 potential proteins targetted by the vaccine, of which 60 proteins were selected for further analysis based on their prediced subcellullar location and function. Synthetic versions of a subset of 11 of these proteins have been generated. Of these six proteins were formulated into experimental vaccines together with a commercial adjuvant and tested for protection against C. burnetii challenge in an outbred mouse model developed within the project. This identified two vaccine formulations with reproducible protective effects against C. burnetii challenge over three replicated studies. Furthermore, the immunogenicity of the vaccine formulations was demonstrated in sheep, a key target species for the vaccine. This work is now being progressed through additional funding which involves an industrial partner with an interest in commercialising the vaccine. In addition to the two vaccine fomulations above which are based on synthetic proteins, we have developed a new safe and effective vaccine for use in sheep based on inactivated whole bacteria which may be cheaper and safer than the currently licensed Q fever vaccine. A patent has now been filed to cover use of the specific C. burnetii strain as a protective bacterin vaccine. |
Exploitation Route | The results of this project to date have been used to facilitate expanded deployment of currently licensed Q fever vaccines in the field. Identification of C. burnetii proteins targeted by the currently licensed Q fever vaccine has allowed the development of the next generation of Q fever vaccines for use in animals and humans based on synthetic versions of these proteins. In addition, the inactivated whole bacterial vaccine could be taken forward by an industrial partner to determine whether it is similarly protective in goats and cattle, and to further evaluate safety and manufacturing processes. |
Sectors | Agriculture Food and Drink Education Healthcare |
Description | The data generated in this project has been used to extend the license claim of the only commercially available Q fever vaccine for livestock to include sheep as a target species. This applies to both the UK and Europe, having been approved by both the UK Veterinary Medicines Directorate and the European Medicines Agency. This will have both economic and societal impacts. Economic impacts will be realised by increased sales of the vaccine and improved reproductive performance of sheep. Societal impacts will be realised by reduced sheddding of Q fever in vaccinated sheep and consequently less human Q fever infections. |
First Year Of Impact | 2023 |
Sector | Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal Economic |
Description | 22-ICRAD Call 2 - Q-Net-Assess (Improved molecular surveillance and assessment of host adaptation and virulence of Coxiella burnetii in Europe) |
Amount | £2,200,000 (GBP) |
Funding ID | BB/X020142/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2023 |
End | 03/2026 |
Description | Horizon Europe: REPRODIVAC - Next-generation vaccines and diagnostics to prevent livestock reproductive diseases of worldwide impact |
Amount | € 6,000,000 (EUR) |
Funding ID | 101060813 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 06/2022 |
End | 06/2027 |
Description | Quantitative and qualitative analyses of cellular responses to Coxevac vaccine in sheep |
Amount | £157,266 (GBP) |
Organisation | Ceva Sante Animale |
Sector | Private |
Country | France |
Start | 03/2020 |
End | 08/2020 |
Description | System immunology-based identification of blood transcriptional modules correlating to Q fever vaccine antibody responses in goats |
Amount | £196,273 (GBP) |
Organisation | Ceva Sante Animale |
Sector | Private |
Country | France |
Start | 11/2020 |
End | 07/2021 |
Title | Coxiella burnetii ruminant challenge model |
Description | Through this project we have established a Coxiella burnetii challenge model in pregnant sheep.This is the only large animal model of C. burnetii infection in the UK. The model involves the challenge of pregnant ewes at 100 days of gestation with 10^6 infectious mouse dose equivalents of C. burnetii nine mile strain via the sub-cutaneous route within the Moredun High Security Unit, and evaluating pregnancy outcome and bacterial shedding during the periparturient period. As C. burnetii is a hazard group 3 pathogen this work has involved approval by the Health and Safety Executive as well as development of detailed health surveillance protocols for staff working on the project. |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2019 |
Provided To Others? | No |
Impact | This model has allowed us to test the efficacy of C. burnetii vaccines in an appropriate animal host (i.e. ruminants). The data generated from the first study will be used to refine the model to ensure that appropriate numbers of animals are used in subsequent studies, in line with the principles of the 3Rs - Replacement, Reduction and Refinement. |
Title | Development of an outbred mouse model of Coxiella burnetii infection for vaccination studies |
Description | A model has been developed using outbred mice to test the efficacy of experimental Coxiella burnetti subunit vaccines. This model will allow the systematic testing of various vaccination formulations to identify those capable of protecting against subsequent C. burnetii challenge. |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2021 |
Provided To Others? | No |
Impact | This model has been used to evaluate a commercial Q fever vaccine and two experimental subunit vaccine formulations. |
Title | High density whole genome peptide microarrays to interrogate Coxiella burnetii specific antibody responses |
Description | Together with Nimble Therapeutics (https://nimbletherapeutics.com/), peptide microarrays have been developed which cover the complete predicted proteome of all sequenced strains of Coxiella burnetii. The array design is such that 12 individual samples can be interrogated on the same array. Arrays were optimised for cattle, sheep, goats and humans. This allows high throughput analysis of antibody responses to the C. burnetii proteome at the individual animal level, giving the most comprehensive and detailed analysis of C. burnetii-specific antibody responses to date. |
Type Of Material | Technology assay or reagent |
Year Produced | 2020 |
Provided To Others? | No |
Impact | This method has allowed this project to interogate the antibody response to the complete C. burnetii proteome at the individual animal level. The methodology has been included in a funding application which aims to use the technology as part of a programme to develop vaccines against ruminant gastro-intestinal parasites. |
Title | High-throughput peptide ELISA |
Description | A 384-well peptide ELISA has been developed using a liquid handling robotics platform to allow high-throughput screening of serum samples for peptide-specific antibody binding. |
Type Of Material | Technology assay or reagent |
Year Produced | 2019 |
Provided To Others? | No |
Impact | This assay has allowed the rapid validation of peptide antibody binding results from genome wide peptide arrays. This work has allowed us to select specific Coxiella burnetii proteins for inclusion in a prototype protein subunit vaccine. |
Title | Coxiella burnetii peptide array dataset |
Description | This datset provides details of C. burnetii peptides recognised by serum IgG from humans, sheep, goats and cattle infected with C. burnetii, and from sheep and goats vaccinated with a commercial Q fever vaccine. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | No |
Impact | This dataset has been used to identify linear B cell epitopes associated with Q fever vaccination and infection. |
Title | Novel tools to analyse peptide microarray data. |
Description | Methods were developed to interogate peptide microarray data generated at the individual animal level. These methods used a combination of the number of epitopes within an antigen regcognised by antibodies and the proportion of individuals within a group which recognise the antigen. |
Type Of Material | Data analysis technique |
Year Produced | 2020 |
Provided To Others? | No |
Impact | This method has been applied to the peptide microarray dataset generated in the project and will be made available through publication. |
Description | CEVA collaboration on Q fever vaccines |
Organisation | Ceva Sante Animale |
Country | France |
Sector | Private |
PI Contribution | The project team has presented project data to CEVA under a confidentiality agreement. Reagents from sheep which were vaccinated against Q fever as part of this project were provided for a related CEVA project. |
Collaborator Contribution | CEVA attended a project meeting at Moredun Research Institute in January 2020 to discuss potential collaboration on Q fever vaccination. CEVA are now industrial partners in a sucessful EU Horizon Europe funding application to further develop a subunit Q fever vaccine. |
Impact | Funding has been acquired to identify immune correlates of protection for the CEVA Q fever vaccine. Additional EU Horizon Europe funding has been acquired with CEVA as the industrial partner. |
Start Year | 2019 |
Description | Characterisation of a novel Coxiella burnetii vaccine strain |
Organisation | Slovak Academy of Sciences |
Department | Institute of Virology |
Country | Slovakia |
Sector | Academic/University |
PI Contribution | We have identified a protective effect of a C. burnetii bacterin vaccine against Q fever. We will now characterise the strain used to manufacure the vaccine in detail and deposit to an appropriate cell culture repository in order to file a patent on this strain. |
Collaborator Contribution | The partner at the Slovak Academy of Sciences, the original owner of the strain, has prepared the isolate and shipped to Moredun Research Institute for characterisation. |
Impact | The vaccine strain has been shipped to Moredun Research Institute and has been characterised by short-read whole genome sequencing. |
Start Year | 2021 |
Description | Enhanced molecular surveillance for Q fever |
Organisation | Animal and Plant Health Agency |
Country | United Kingdom |
Sector | Public |
PI Contribution | This collaboration has been established to allow us to better understand strain types of Coxiella burnetii associated with ruminant clinical disease in the UK. C. burnetii positive diagnostic material will be provided by APHA (the UK National Reference Laboratory for Q fever) to Moredun Research Insitute for C. burnetii isolation and Whole Genome Sequencing (WGS). |
Collaborator Contribution | The partner has agree to supply C. burnetii positive diagnostic material for bacterial isolation and molecular (WGS) characterisation. |
Impact | This collaboration has resulted in an ICRAD (International Coordination of Research on Infectious Animal Diseases) funding bid to develop an European-wide (Germany, Spain, France, Belgium, the Netherlands) molecular surveillance system for Coxiella burnetii involving European Q fever Reference Laboratories, veterinarians and research scientistis |
Start Year | 2021 |
Description | Evaluation of a candidate International Standard for human anti-Q fever IgG |
Organisation | National Institute for Biological Standards and Control (NIBSC) |
Country | United Kingdom |
PI Contribution | We have evaluated a positive control standard for human anti-Q fever IgG on standard serological assays (ELISA/IFA) |
Collaborator Contribution | NIBSC-MHRA and the WHO believes that there is a need for the preparation of various reference standards for the diagnosis of Q fever infections, for the evaluation of immune status, as a reference reagent for functional in vitro and immune-assays and for the harmonisation of these assays across laboratories. NIBSC have provided a positive control standard for evaluation at Moredun Research Institute. |
Impact | ELISA and IFA data generated from a new International Standard for human anti-Q fever IgG. |
Start Year | 2021 |
Description | Further development of a safe and effective Coxiella burnetii bacterin vaccine |
Organisation | Slovak Academy of Sciences |
Department | Biomedical Research Center |
Country | Slovakia |
Sector | Academic/University |
PI Contribution | We have performed a detailed characterisation of a C. burnetii strain provided by the collaborator at the Slovak Academy of Sciences, including genomic analysis and LPS characterisation. |
Collaborator Contribution | The partner has provided a key C. burnetii strain under an MTA for further development of a Q fever vaccine based on inactivated C. burnetii. The partner has also provided information on the propagation of the bacterin strain for these studies. |
Impact | This work will progress towards a patent filing. |
Start Year | 2020 |
Description | Immunogenicity and safety characterization of Q fever vaccines using systems immunology |
Organisation | University of Bern |
Country | Switzerland |
Sector | Academic/University |
PI Contribution | This collaborative research project involved the characterisation of two Q fever vaccine formulations in goats using serological, clinical and transcripomic approaches. Moredun Research Institute led the project, performed animal studies, clinical and serological analyses and prepared blood leukocyte RNA for sequencing at the University of Bern. |
Collaborator Contribution | University of Bern performed RNAseq analysis of blood leukocytes and analysed data using a Blood Transcriptional Module (BTM) approach. BTM induced by the different vaccine formulations were compared and related to clinical and serological data. |
Impact | A project report has been submitted to the funder which is currently confidential. |
Start Year | 2021 |
Description | Q-GAPS consortium partnership |
Organisation | Friedrich Loeffler Institute |
Department | Federal Research Institute for Animal Health |
Country | Germany |
Sector | Academic/University |
PI Contribution | Q-GAPS (Q fever GermAn Interdisciplinary Program for reSearch) is an interdisciplinary and unique consortium is committed to investigate unsolved questions relating to the epidemiology, immunology, pathogenesis, surveillance and control of Coxiella burnetii. We have presented project data to the Q-GAPS consortium members in Glasgow (Septeimber 2019) which has resulted in an invitation to present at the Q-GAPS consortium meeting in Munich. |
Collaborator Contribution | Q-GAPS partners have organised a consortium meeting in Munich (March 2020) at which the PI from this grant (Dr Tom McNeilly) will present. |
Impact | Initial outcomes have centred around knowlegde exchange, with a view to collaborating on Q fever vaccination and diagnostics with members of the Q-GAPS consortium. |
Start Year | 2020 |
Title | Phase II Vaccine |
Description | Development of a bacterin vaccine for Q fever based on an inactivated phase II Coxiella burnetii strain. |
IP Reference | PCT/GB2023/053101 |
Protection | Patent / Patent application |
Year Protection Granted | 2022 |
Licensed | No |
Impact | Discussions on licensing the technology to a commercial partner for development of a commercial phase II Q fever vaccine. |
Description | 6th European Meeting of Animal Chlamydioses & Zoonoses (EMAC-6): Presentation on Q fever vaccines development and genetic diversity of Coxiella burnetii. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | A talk was given on the development of subunit Q fever vaccines and how these can be integrated into molecular surveillance programmes for Q fever. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.um.es/esacz/meetings.html |
Description | Accelerated development of a safe and easily manufactured Q fever vaccine |
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 | A poster was presented at the UK & International Veterinary Vaccinology Network Conference 2019 in London, UK. The postier outlined the Q fever vaccine project and current progress on the first vaccination trial. This was attended by over 200 national and international researchers from North and South America, Africa, Asia and Australasia. The poster was awarded third prize and sucessfully instigated questions and discussions on the project. The meeting also allowed introductions to the African Vaccinology Network (AfVANET) coordinators to discuss potential future research collaborations. |
Year(s) Of Engagement Activity | 2019 |
URL | https://drive.google.com/file/d/1RReamwdNnCoZZmNWZJeGtC6mApcyY9q_/view |
Description | FLI (Friedrich-Loeffler-Institut) Invited seminar on ruminant Q fever vaccine development |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | A virtual seminar was given to FLI scientists and students on the use of high density peptide microarrays to interrogate protective antibody responses induced by protective Q fever vaccines. The work attracted considerable interest, particular in terms of the pregant ewe challenge model used to evaluate Q fever vaccines.This stimulated future collaborative research which is now being funded by a large EU Horizon Europe project grant. |
Year(s) Of Engagement Activity | 2021 |
Description | IBAHCM seminar series talk: Ruminant bacterial zoonoses: pathogen diversity, immunity and vaccine interventions |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | An invited seminar was given by Tom McNeilly as part of the University of Glasgow Institute of Biodiversity, Animal Health & Comparative Medicine (IBAHCM) seminar series entitled: Ruminant bacterial zoonoses: pathogen diversity, immunity and vaccine interventions. Approximately 40 people attended the seminar, including a mixture of undergraduate, post-graduate students, research professionals and visiting researchers. The talk covered Q fever vaccination and the latest results from this project. A member of the audience was part of the German Q-GAPS consortium (https://www.q-gaps.de/en/) and as a result of this talk, a collaboration has now been established betweeen this project and the Q-GAPS consortium. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.gla.ac.uk/researchinstitutes/bahcm/about/events/instituteseminars/ |
Description | Industry presentation on Q fever vaccine development |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | A presentation on Q fever vaccine development was given to a veterinary pharmaceutical company. This involved the R&D and marketing team of the company. The company requested more information on the vaccine to consider the commercial opportunities of a new Q fever vaccine for small ruminants. |
Year(s) Of Engagement Activity | 2022 |
Description | International Veterinary Vaccinology Network Newsletter |
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 | An article was written for the International Veterinary Vaccinology Newsletter to promote the project. The article gave an overview of the project including background on Q fever and details of the programme of work. This resulted in a number of queries regarding potential collaborations on projects related to Q fever vaccines which are being actively pursued. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.intvetvaccnet.co.uk/news/2018/10/researchers-awarded-funding-develop-improved-q-fever-va... |
Description | International Veterinary Vaccinology Network Vaccines for Ruminants Symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | This symposium was virual given COVID-19 restrictions. A presentation was given on Q-fever: the use of a pregnant ewe challenge model to assess the efficacy of phase I and phase II Coxiella burnetii bacterin vaccines in sheep. Attendees were research scientists and other stakeholders (e.g. vaccine manufacurers) with up to 100 delgates attending from an international audience. The presentation covered Q fever vaccine efficacy testing and the use of high density peptide microarrays to interogate vaccine-induced antibody responses |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.intvetvaccnet.co.uk/events/ivvn-virtual-symposia/vaccines-for-ruminants |
Description | Moredun Magazine article: "New grant to develop improved Q fever vaccines" |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | An article was written for the Moredun Magazine Autumn/Winter 2019. This magazine is distributed to all Moredun Foundation members (>10,000). The article gave a background on Q fever and outlined the approach taken in the project to develop a safer Q fever vaccine. The article prompted questions and discussions to the project PI by members of the Moredun group board. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.moredun.org.uk/publications/moredun-magazine |
Description | Open Access Government article: "Q fever: An emerging problem in LMIC and the need for improved vaccines" |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | A magazine article was published in Open Access Government on Q fever: An emerging problem in LMIC and the need for improved vaccines. This article was targetted at policy makers/government agencies to highlight the increasing awareness of Q fever in LMIC countries and the need to develop safer and more easily manufactured vaccines. The article linked to the project (BB/R019975/1) and initiated contacts with potential collaborators in LMIC countries. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.openaccessgovernment.org/improved-vaccines/62803/ |
Description | Poster presentation at the 12th Annual Edinburgh Infectious Diseases Symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | A poster was presented on genetic diversity of Coxiella burnetii and how this information is being used to develop next generation Q fever vaccines. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.ed.ac.uk/edinburgh-infectious-diseases/news/news/12th-annual-symposium |
Description | Presentation at Moredun Research Institute External Science Review Day June 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | The post-doctoral research scientist employed on the project, Dr Sarah Williams-MacDonald, gave a talk on "Accelerated development of a safe and easily manufactured Q fever vaccine". This talk gave an update on the project results up to June 2020. |
Year(s) Of Engagement Activity | 2019 |
Description | Presentation at the 73rd Annual Association for Veterinary Teachers and Research Workers Conference 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | A short talk and poster presentation was given at this meeting on the Q fever project by the post-doctoral research scientist employed on the project. Approximately 40 people attended the conference, mainly post-graduate research scientists from the UK veterinary research community. The talk and poster initiated discussions on existing Q fever vaccines and how these can be improved in terms of safety of manufacture and use. |
Year(s) Of Engagement Activity | 2019 |
URL | http://www.avtrw.co.uk/past-events/2019/ |
Description | Q-GAPS semiar on Q fever vaccines for ruminants |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | A on-line presentation was given to the Q-GAPS (Q fever GermAn Interdisciplinary Program for reSearch) consortium annual meeting on the use of high-density peptide microarrays to identify Coxiella burnetii antigens targetted by protective anitbody responses. The talk also provided an update on the latest Q fever vaccine research and animal models of Q fever. The consortium included approximately 50 research scientisits, veterinarians and medical practitioners. |
Year(s) Of Engagement Activity | 2021 |
URL | https://q-gaps.de/en/ |
Description | Seminar presentation at the Friedrich Loeffler Institute, Jena, Germany, on Q fever vaccine development and genetic diversity of Coxiella burnetii. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | A seminar was given on the development of subunit vaccines to control Coxiella burnetii infections in livestock using reverse vaccination approaches, and how the understanding the genetic diversity of C. burnetii is critical for this work. |
Year(s) Of Engagement Activity | 2023 |
Description | The contribution of livestock to food production, biodiversity and the environment - Open Day in the presence of HRH The Princess Royal |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | An open day event was held on 21st October 2019 at the Moredun Research Institute on 'The contribution of livestock to food production, biodiversity and the environment'. The Q fever vaccine project was presented to HRH The Princess Royal and her visiting group and the project aims and outputs discussed. A total of 114 people attended the meeting including invited members of the general public, farmers, veterinarians, scientists, undergraduate and postgraduate students. The presentation sparked discussions on the current state of Q fever vaccines and how they can be improved. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.moredun.org.uk/news/press-release-princess-royal-visits-moredun-highlight-contribution-l... |
Description | Use of high density peptide arrays to understand vaccine-specific antibody responses |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | 50 people attended this webinar of which ~20 were undergraduate or post-graduate students. The pepide array methodology developed in this project was presented, which prompted questions from the audience in terms of its application to other vaccine research programmes. |
Year(s) Of Engagement Activity | 2021 |