Edinburgh Research Explorer Construction of generic roadmaps for the strategic coordination of global research into infectious diseases of animals and zoonoses

The Strategic Alliance for Research into Infectious Diseases of Animals and Zoonoses (STAR-IDAZ) International Research Consortium (IRC) coordinates global animal health research to accelerate delivery of disease control tools and strategies. With this vision, STAR-IDAZ IRC has constructed four generic research roadmaps for the development of candidate vaccines, diagnostic tests, therapeutics and control strategies for animal diseases. The roadmaps for vaccines, diagnostic tests and therapeutics lead towards a desired target product profile (TPP). These interactive roadmaps describe the building blocks and for each the key research questions, dependencies, challenges and possible solution routes to identify the basic research needed for translation to the TPP. The control strategies roadmap encompasses the vaccine, diagnostic tests, and therapeutic roadmaps within a wider framework focusing on the inter-dependence of multiple tools and knowledge to control diseases for the benefit of animal and human health. The roadmaps are now being completed for specific diseases and complemented by state-of-the-art information on relevant projects and publications to ensure that the necessary research gaps are addressed for selected priority diseases.

the wildlife-livestock-human interfaces are important drivers for emergence and transmission of zoonotic diseases (Taylor, Latham, & Woolhouse, 2001). Control of animal diseases can therefore have wide-ranging health and socio-economic impacts on humans such as cost-effective provision of food, reductions in water-borne diseases and financial survival of rural populations. The handling and consumption of uncooked contaminated livestock products compromise food safety and pose potential risks of zoonotic disease transmission (van den Brom, de Jong, van Engelen, Heuvelink, & Vellema, 2020). Antimicrobial resistance (AMR) in humans is inter-linked with AMR in farm animals and in the wider environment (Woolhouse, Ward, van Bunnik, & Farrar, 2015). Finally, control of infectious diseases in ruminant livestock can reduce methane emissions by as much as 33% thereby mitigating against climate change (Fox, Smith, Houdijk, Athanasiadou, & Hutchings, 2018).
These grand challenges call for solutions requiring co-ordinated, cross-disciplinary approaches involving multiple stakeholders, that needs to cooperate for the collective good (http://www. Here, we describe the construction of four generic STAR-IDAZ IRC roadmaps for the development of candidate vaccines, diagnostic tests, therapeutics and disease control strategies. We explain how these generic roadmaps can be applied to develop disease-specific roadmaps that can be ultimately translated into the development of novel tools and strategies for disease control.

| CON S TRUC TI ON OF THE G ENERI C S TAR-IDA Z IRC ROADMAPS
The four generic roadmaps were constructed by considering the desired endpoint, which could be a target product profile (TPP) or a control strategy, and working back through the steps that are essential for reaching that endpoint. This creates a continuous pipeline that encompasses basic and translational scientific research to deliver the goal. Each step on the roadmaps is shown as a distinct node. Each node defines a criterion/theme that is essential for progressing towards the final goal. The generic roadmaps have been designed to be broadly applicable to the STAR-IDAZ IRC priority diseases to be fit for purpose. There are two exceptions to this which are described below.
To avoid the roadmaps becoming overly complicated, criteria/ themes were only assigned to nodes if they constituted a major barrier to progression to the final goal. Certain nodes have subthemes but only where these are inter-related to each other and the overarching theme. Each node is populated with five 'Lead' areas that highlight the knowns and unknowns for the issue in question.
These are as follows: (1) research question; (2) challenge; (3) solution routes; (4) dependency notes; and (5) state of the art. Each Lead has an over-arching question and/or statement of intent with supporting information that is designed to focus research efforts ( Figure 1).
The STAR-IDAZ IRC generic roadmaps can be accessed here: https://roadm aps-public.star-idaz.net/#/home. The roadmaps are interactive and by placing the cursor above a given node, the direction of travel of nodes that feed into that node will appear. The four generic roadmaps are described in the subsections below.

| Roadmap for the development of candidate vaccines
Vaccination is a well-established and sustainable strategy for the prevention and control of infectious diseases and the enormous contribution that vaccines have made to societal health cannot be underestimated. Indeed, they have been described as 'an achievement of civilization, a human right, our health for the future' (Rappuoli,

F I G U R E 1
The five Lead areas listed under each node on the generic roadmaps. Each Lead has an overarching question and/or contains information on the current state of knowledge with the collective aim of focusing research efforts towards the desired goal.

Research question:
What are we trying to achieve and why? What is the problem we are trying to solve?

Challenge:
What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

Solution routes:
What approaches could/should be taken to address the research question?

Dependency notes:
What else need to be done before we can solve this need?

State-of-the-art:
Existing knowledge including successes and failures Santoni, & Mantovani, 2019). Early vaccines were developed 'empirically' rather than 'rationally', relying on growth of the organism to produce the vaccine antigen (De Gregorio & Rappuoli, 2014). In learning from past success, we must adapt, develop, exploit and apply technological advances to new approaches to vaccinology to deal with evolving threats to global health (Andreano, D'Oro, Rappuoli, & Finco, 2019). There are many criteria that a successful vaccine must meet. While safety and efficacy are foremost, vaccines need to be stable, cost-effective and easy to deliver to the target population. These criteria need to be considered in the TPP and the earlier in the research pipeline that these criteria are identified, the greater the likelihood of developing a vaccine that meets the targeted stakeholder needs.
While there are different types of vaccines (attenuated organisms, inactivated organisms, genetic, subunit and vectored), there are a number of common criteria that need to be considered for all.
These are safety, delivery route, delivery platform and efficacy in a challenge model ( Figure 2). These four criteria are examples of inter-related sub-themes within a common theme as described above.
The choice of vaccine type depends on a number of factors that are not common to all. Thus, the attenuated vaccine nodes are linked to identification of virulence factors node but are not to adjuvants whereas the opposite is true for subunit vaccines. This reflects the relative co-dependencies of these nodes. Likewise, knowledge of protective antigens has different dependencies for different vaccine types. A notable advantage of veterinary vaccine research compared to human is the experimental challenge model to evaluate efficacy.
In veterinary species, this is usually conducted in the target species which avoids the translational step from a biomedical model into the target species. This provides opportunities to study immune responses to both vaccination and challenge in the natural host (Entrican, Wattegedera, & Griffiths, 2015).

| Roadmap for the development of diagnostic tests
The reliable identification of infected animals is a fundamental component of effective disease control strategies. It also underpins many government policies for the movement and trade of animals and animal products (Holm, Hill, Farsang, & Jungback, 2019

| Roadmap for the development of therapeutics
While 'prevention is better than cure' is a highly desirable goal in disease control, it is not always easy to achieve. Depending on the policies for different livestock diseases, this can mean culling or treatment. Antibiotics and antiparasitics are common therapeutics for control of livestock diseases, and both are used extensively in animal production systems. However, their deployment needs to be carefully managed to maximize impact while minimizing potential adverse effects in animals, humans and on the environment (Vercruysse et al., 2018;Woolhouse et al., 2015). Despite the emergence of AMR and the development of new vaccines that can help to reduce the use of antibiotics (Hoelzer et al., 2018), new therapeutic options (e.g. antimicrobial peptides, phages and immunostimulants) will be needed to preserve animal health and welfare (Seal, Lillehoj, Donovan, & Gay, 2013). The control of parasitic helminths is heavily reliant on therapeutics due to the difficulties in developing effective prophylactic vaccines. However, anthelminthic resistance is making parasite control increasingly more difficult, hence the need to develop new treatments and control strategies (Vercruysse et al., 2018). The STAR-IDAZ IRC roadmap for developing new therapeutics is shown in Figure 4.
Once again, the starting point for development of a novel therapeutic is the TPP and it is identified within the five Leads under the 'therapeutic' node. Practical steps in the process involve chemistry, risk assessment methodologies and clinical testing.
In turn, these are dependent on more basic knowledge of hostpathogen interactions and mode of action that allow screening of compound libraries for identification of potential target compounds for evaluation in animal models for pharmacokinetics and efficacy ( Figure 4).

| Roadmap for the development of disease control strategies
The roadmaps for candidate vaccines, diagnostics and therapeutics have all been designed with a TPP in mind (Figures 2-4). However, the roadmap for development of disease control strategies has been constructed to provide an over-arching framework that integrates the multiple components of successful disease control strategies.
This includes vaccines, diagnostic tests and therapeutics that all feed into the 'control tools' node either directly or indirectly. Thus, the F I G U R E 3 Roadmap for the development of diagnostic tests. The interactive diagnostic test development roadmap can be found at https://roadm aps-public.star-idaz.net/#/yuBvI three other generic roadmaps can be directly accessed via the disease control roadmap by clicking on their ascribed nodes ( Figure 5).
The roadmap incorporates socio-economic and environmental (including farming system) aspects of disease control. The uptake and

F I G U R E 4
Roadmap for the development of therapeutics. The interactive therapeutic development roadmap can be found at https:// roadm aps-public.star-idaz.net/#/bUDor F I G U R E 5 Roadmap for the development of control strategies. The outcome of the control strategies roadmap (blue) also incorporates the other three generic roadmaps (green). The interactive control strategies roadmap can be found at https://roadm aps-public.star-idaz. net/#/XkjSS implementation of control strategies are dependent on the socio-economic factors; hence, these are closely linked on the roadmap and need to be considered at an early stage of development (Charlier & Barkema, 2018). The roadmap takes into account disease surveillance, epidemiology and modelling that are linked back to the basic science that generates knowledge on infection status, host range, pathogen genome and also host genetics. Depending on the disease in question and the tools available (or under development), control strategies also include contact tracing of animals, segregation of infected animals and culling. As for the previous roadmaps, the basic scientific research will be driven by an awareness of the ultimate translational goal, which in this case is a practical and effective disease control strategy.

| APPLI C ATI ON OF THE G ENERI C ROADMAPS TO THE S TAR-IDA Z IRC PRI ORIT Y D IS E A S E S
In addition to the generic roadmaps described above, the STAR-IDAZ IRC has been developing roadmaps for its priority diseases. These Network (UKVN) which has adopted a systematic approach to prioritize vaccinology research into animal pathogens with human epidemic potential (Noad et al., 2019). The approach took into account the stage of vaccine development for each pathogen which could then be mapped to a pipeline using an interactive tool that identifies bottlenecks in vaccine development with a focus on the TPP. The underlying principle is that the identification of these rate-limiting bottlenecks allows funders to take corrective action by directing their strategies accordingly (Drury, Jolliffe, & Mukhopadhyay, 2019). The DHSC UKVN funding is primarily (but not exclusively) focussed on human vaccine development as there is also recognition that disease control in the animal host will reduce transmission of infection to humans. Consequently, DHSC UKVN has therefore developed an equivalent pipeline tool for veterinary vaccine development (Francis, 2020). This tool shares conceptual similarities with the STAR-IDAZ IRC vaccine roadmap, but differs by incorporating regulatory processes in the pipeline process. The STAR-IDAZ IRC generic roadmaps address fundamental and translational research priorities for animal diseases and consider not only vaccine development, but also the development of accompanying diagnostics, therapeutics and key scientific information that could lead to more effective control strategies.
In conclusion, the four generic STAR-IDAZ IRC roadmaps described here are designed to highlight gaps in knowledge and capability that then focus research activities that address those gaps and advance the control of infectious diseases of animals and zoonoses.
These roadmaps should therefore be used by research funders and donors in the development of research calls, as well as by researchers at an early stage of preparing funding proposals to speed up the delivery of innovative control tools against priority animal diseases.

ACK N OWLED G EM ENTS
We thank all members of the STAR-IDAZ IRC Scientific Committee

CO N FLI C T O F I NTE R E S T
None identified.

E TH I C A L A PPROVA L
The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required as this is an article describing the development of online tools with no original research data.

DATA AVA I L A B I L I T Y S TAT E M E N T
This article does not contain original scientific research data. All of the online tools described are publicly accessible via the hyperlinks provided within the Figure legends.