PERSPECTIVES adjuvant combinations to inform ‘go’ or ‘no- go’ decisions with regard to subsequent Using cross- species vaccination development of promising vaccine candidates (Fig. 1). approaches to counter emerging Most human infectious diseases have an animal origin, with more than 70% of infectious diseases emerging infectious diseases that affect humans initially crossing over from 8 George M. Warimwe , Michael J. Francis , Thomas A. Bowden, animals . Generating wider knowledge of how pathogens behave in animals can Samuel M. Thumbi and Bryan Charleston give indications of how to develop control Abstract | Since the initial use of vaccination in the eighteenth century, our strategies for human diseases, and vice understanding of human and animal immunology has greatly advanced and a wide versa. ‘One Health vaccinology’, a concept in which synergies in human and veterinary range of vaccine technologies and delivery systems have been developed. The immunology are identified and exploited COVID-19 pandemic response leveraged these innovations to enable rapid for vaccine development, could transform development of candidate vaccines within weeks of the viral genetic sequence our ability to control such emerging being made available. The development of vaccines to tackle emerging infectious infectious diseases. Due to similarities in diseases is a priority for the World Health Organization and other global entities. host–pathogen interactions, the natural More than 70% of emerging infectious diseases are acquired from animals, with animal hosts of a zoonotic infection may be the most appropriate model to study the some causing illness and death in both humans and the respective animal host. Yet disease and evaluate vaccine performance9. the study of critical host–pathogen interactions and the underlying immune This could result in a scenario where a mechanisms to inform the development of vaccines for their control is traditionally cross- species vaccine is feasible, such as done in medical and veterinary immunology ‘silos’. In this Perspective, we highlight Louis Pasteur’s live attenuated rabies vaccine 10 a ‘One Health vaccinology’ approach and discuss some key areas of synergy in that was protective in dogs and humans — although different products are now human and veterinary vaccinology that could be exploited to accelerate the used for rabies vaccination in humans and development of effective vaccines against these shared health threats. dogs11 — or our own group’s Rift Valley fever vaccine, which is in co-development Vaccination to control infectious diseases as common bottlenecks that influence for use in humans and multiple livestock has had a major direct impact on human the success of vaccine development species12. Effective control of zoonotic health and welfare and has also secured programmes6 (Fig. 1). However, there are diseases may require vaccination within food supply by improving animal health and differences in the complexity of the vaccine reservoir animal hosts to break transmission controlling zoonotic diseases. For instance, pipelines, largely due to the differing types to humans, and in humans to prevent childhood vaccination prevents more than of clinical data and regulatory requirements disease13, making One Health vaccinology 2 million deaths every year, with vaccination for licensure and the associated bottlenecks relevant for disease control policy. This coverage being a strong indicator of the that are unique to the animal or human strategy is already used for prevention incidence of vaccine-preventable diseases in vaccine pipeline6. One example is the and elimination of rabies, where mass dog humans (for example, measles, yellow fever need for vaccine safety and efficacy data vaccination remains the most cost-effective and polio)1. Similarly, veterinary vaccination as assessed by experimental infection strategy for breaking disease transmission to against endemic diseases increases survival of vaccinated and unvaccinated target humans14,15. However, due to the difficulty in and productivity in food- producing animals animal species in the veterinary field; in predicting spillover events for new infections such as cattle and poultry, with net gains in humans, phase II and phase III randomized from animals to humans16, implementing a disposable household income and access to controlled studies for estimation of cross- species vaccination programme may protein- rich animal source foods improving vaccine efficacy against natural exposure only be feasible where the domestic animal human nutrition2–5. However, despite these are used, although human infection reservoir of human infection is known and many other examples of vaccine impact, studies are now used for some vaccine (see Table 1 for some examples), but a very little interaction occurs between programmes7. Despite these differences, cost–benefit analysis would be necessary human and animal vaccine developers and the solutions to address bottlenecks in the to inform implementation. policymakers. animal and human vaccine development For non- zoonotic illnesses, the natural The development pipelines for human pipelines tend to be similar6. For instance, course of infection and acquisition of and animal vaccines are similar processes, optimizing the immunogenicity of vaccines, immunity against closely related pathogens including biological and scientific parallels whether in animals or in humans, involves may be similar between animals and in vaccine design and evaluation, as well iterative study of vaccination regimens or humans, allowing accelerated development NATURE REVIEWS | IMMUNOLOGY 0123456789();: PERSPECTIVES Human vaccine pipeline Preclinical study Phase I Phase I–III (10–15 years, ≥US$1 billion) (laboratory animals) (first-in- (large-scale human trial) population studies) Licensure and deployment Target product Immunogen GMP process Continuous safety monitoring profile design development (pharmacovigilance/phase IV studies) and manufacture Veterinary vaccine pipeline (3–6 years, ≥US$0.015 billion) Licensure and deployment Early-phase development Late-phase development/ (safety and efficacy in field trials natural disease host) (farm-level vaccine studies) Regulatory affairs and ethical approvals Fig. 1 | Vaccine development pipeline. The typical vaccine development pipeline is shown, starting from target product profiling to licensure and deployment. The respective stages and approximate costs for veterinary and human vaccines are shown. Although presented as a linear chronological process, some of the different stages of the pipeline for a ‘multispecies’ vaccine can occur in parallel. For instance, the candidate ChAdOx1 RVF vaccine against Rift Valley fever12 will soon undergo evaluation in human clinical trials in parallel with veterinary development, having been made with the same manufacturing starting material. GMP, good manufacturing practice. of vaccines that target similar protective relatedness for vaccine development and deployment of effective vaccines against mechanisms. For example, bovine and was the basis of the vaccine that was used for zoonotic diseases. We focus on comparative human respiratory syncytial viruses, which eradication of smallpox22. immunology, applications of current vaccine cause pneumonia in young calves and Early manufacture of Jenner’s smallpox technologies, and regulatory and operational children, respectively, are closely related vaccine involved serial propagation of the considerations for vaccine deployment. genetically and are targeted by the same cowpox virus in calves reared in ‘vaccine types of immune mechanisms, suggesting farms’23. Vaccine manufacture has advanced Immune systems of different species that vaccine strategies exploiting the same considerably but animal-sourced materials The overall structure and composition of the underlying mechanism of immunity may are still used for production of human innate and adaptive immune systems of work for both species17,18. The most widely vaccines; for example, embryonated chicken humans and animal species are broadly used human vaccine, bacille Calmette– eggs are routinely used for the manufacture similar, and comparing their responses Guérin (BCG) against tuberculosis, is of influenza and yellow fever vaccines24,25. to inoculation or infection with similar essentially an attenuated strain of the New highly scalable platform technologies antigens or pathogens can inform vaccine cattle- infecting bacterium Mycobacterium and delivery systems are accelerating vaccine development34. Allometric scaling is an bovis that is avirulent in a wide range of development such that it is now possible important consideration, and the body animal species19. BCG was developed to go from the pathogen genetic sequence size and physiology of livestock species through close collaboration between medical encoding an immunogen of choice to a are more similar to those of humans and veterinary practitioners more than vaccine candidate in a matter of weeks26. than to those of rodents. While rodents 100 years ago19, and the extensive experience Bioinformatic analyses, X- ray crystallography may be convenient for laboratory studies of its use in humans is now informing and cryo- electron microscopy continue due to the ready availability of specific vaccination strategies to control tuberculosis to be leveraged for the identification immunological reagents, lower purchase in cattle20. A recent study found that BCG and optimization of protective antigens and maintenance costs