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adjuvant combinations to inform ‘go’ or ‘no-​go’ decisions with regard to subsequent Using cross-​species development of promising 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 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 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 ’s live attenuated 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 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, 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

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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 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 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 and ease of handling, vaccination in humans also confers for human and veterinary vaccines27–29. they may not reproduce the pathology protection against other non-tuberculous​ These new technologies are being applied and immunological attributes that would infections in early childhood21; we are aware to emerging infectious diseases such as be observed in a natural animal host of no studies of non-specific​ effects of BCG COVID-19 or stubborn persistent challenges, of infection9. The similarities between vaccination in cattle, but this clearly warrants including malaria and brucellosis30–33. humans and livestock species may be most investigation. ’s observation In this Perspective, we highlight important when one is comparing the that milkmaids exposed to the cowpox virus some key areas of synergy in human and responses to aerosol delivery of antigens or were protected against smallpox is perhaps veterinary vaccinology that could be pathogens35. Clearly, non-human​ primates the earliest example of exploiting pathogen exploited to accelerate the development and are ideal species to predict responses in

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humans, but their availability is limited a case to be made that the results of vaccine responses is in determining the role and certainly not possible for field studies. efficacy and safety studies in large animals of antibodies with long heavy chain Nevertheless, the differences between the can provide important information to help complementarity-​determining region 3 immune systems of humans and animals shape vaccine development programmes (CDR H3) gene segments. Human antibody are important, and a cautious approach in humans, but the precise immune CDR H3 ranges between 8 and 16 amino is justified when one is drawing detailed mechanisms conferring that resistance acids in length, although antibodies with conclusions from animal studies. may be different between species. longer CDR H3 have been observed (for Some of the most striking differences The similarities between human and example, 18 amino acids56 and 28 amino between the immune systems of humans and bovine tuberculosis offer a potential acids57) and seem to play an important animals relate to their T cell populations opportunity for cross-species​ development role in cross-protective​ immune responses and antibody structures (Fig. 2). Pigs of novel vaccines against the diseases. to HIV-1 (refs56,57). However, such long are increasingly used to study vaccine A BCG challenge model has been used CDR H3 antibodies are rare in humans, candidates, in particular influenza to investigate the protective immune which makes some investigations more vaccines36–38. However, there are key response in humans. Genes linked to challenging58. By contrast, cattle have a differences between pigs and humans that protective responses included IFNG and larger population of antibodies (more than should be kept in mind. For example, three IL17F, together with other genes associated 10% of antibodies) with long and ultralong distinct subpopulations of CD8+ T cells have with these cytokines that those two genes (more than 70 amino acids) CDR H3 gene been identified in pigs by flow cytometry: encode, such as NOD2, IL22, IL23A and segments59, and the study of these ultralong a bright-​staining population that expresses FCGR1B50. A recent review highlights the cattle antibodies may prove useful for the the CD8αβ heterodimer, a population that potential role of IL-22 in the protective development of human interventions. expresses the CD8αα homodimer and a response to Mycobacterium tuberculosis For instance, immunizing cattle with HIV CD8+ population that co-expresses​ CD4 infection in cattle and humans51. In cattle, envelope glycoprotein results in rapid (refs39–41). Ongoing studies indicate that IL-22 and IFNγ produced by purified induction of broadly neutralizing ultralong most memory T cells in pigs are present in protein derivative-stimulated​ peripheral CDR H3 antibodies, whereas it takes the double-positive​ population and that this blood mononuclear cells were identified as many years for such broadly neutralizing population is the predominant source of the primary predictors of vaccine-induced​ antibodies to develop in humans following interferon-​γ (IFNγ) in recall responses to protection in an M. bovis challenge model52. HIV infection60. These bovine antibodies live viral vaccines39,42. Peripheral CD4+CD8+ Furthermore, BCG vaccination in children may be engineered for prophylactic or T cells have been characterized in many and young calves provides protection therapeutic use, and determining the different species but the proportion of these against tuberculosis, with activation of immune mechanisms that underlie their cells in the total T cell population differs natural killer cells being a key immune induction could inform vaccine design. greatly, from 1–2% in humans to 10–20% in mechanism in the induction of protective Conversely, the antibody repertoire pigs. In humans, the number and function of immunity in both species53,54. Therefore, in dromedary camels is composed of this subpopulation change in response to a there are elements of the protective immune both conventional IgG molecules and range of infectious and neoplastic diseases43. response to tuberculosis that are consistent heavy chain-only​ IgG antibodies (HCAb) Recently, these double-positive​ human between cattle and humans, including molecules, with the latter accounting for T cells were shown to exhibit a memory humoral responses55. The similarities in more than 70% of the repertoire61. These phenotype44, similar to the double-positive​ different species of immune responses to smaller HCAb molecules are better adapted T cells in pigs. The impact on responses closely related pathogens may help identify for binding cryptic epitopes on pathogens to vaccination and infection due to the protective vaccine responses. that may be inaccessible to conventional marked difference in the proportion of these Another example where studying IgG molecules62, allowing their use in double-​positive cells in different species is comparative immunology may improve diverse applications in diagnostics, therapy yet to be resolved. our understanding of protective immune and research62. However, very little is Another striking difference is the large percentage of circulating γδ T cells in young Table 1 | Key diseases where cross-species​ vaccination programmes may be feasible pigs and ruminants. γδ T cells constitute up to 60% of circulating lymphocytes in Human disease Key domestic animal hosts licensed licensed young cattle45 and pigs46. Even in adulthood, human vaccines veterinary available? vaccines available? 30% of the peripheral blood mononuclear cells found in these species are γδ T cells47, Rabies Dogs Yes Yes whereas in humans only approximately Rift Valley fever Sheep, goats, cattle, camels No Yes 4% of peripheral blood mononuclear cells Brucellosis Sheep, goats, cattle, camels No Yes are γδ T cells48. Despite this difference Crimean–Congo Sheep, goats, cattle, camels No No between humans and ruminants, the haemorrhagic fever results of protection studies in ruminants can provide valuable evidence to support Middle East Camels No No respiratory syndrome the development of human vaccines; for example, the protection of calves from Tuberculosis Cattle Yes No bovine respiratory syncytial virus by a Sheep, goats, cattle, camels Yes No stabilized prefusion F protein vaccine may Nipah virus infection Pigs No No guide the development of human vaccines Hendra virus infection Horses No Yes against respiratory syncytial virus49. There is

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in stubborn pockets of each disease67,68. a b c d The endgame for these programmes required innovative strategies that included house-​to-house​ case searches for smallpox and containment of outbreaks, and participatory community-based​ surveillance approaches to identify the hidden rinderpest disease pockets and deploy the vaccines. The key similarities in the deployment Camelid/VHH of vaccines and cross-learning​ from the (VHH-5) medical and veterinary fields go beyond these disease eradication programmes to the control and elimination of current vaccine-preventable​ diseases. Vaccination for the control of zoonoses Bovine (BLV1H12) Human (PG9) Mouse (93F3) has dual benefits for both human and animal Fig. 2 | The heavy chains of bovine antibodies can encode a very long CDR H3, which contrasts health. A good example is the control with the equivalent CDRs of human, mouse and heavy chain camelid antibodies. Structures of of rabies, a viral transmitted antigen-binding​ fragment regions from bovine (BLV1H12, Protein Data Bank (PDB) ID 4K3D58; part a), to humans through dog bites, which is human (PG9, PDB ID 3U2S86; part b), mouse (93F3, PDB ID 1T4K87; part c) and camelid (VHH-5, PDB ID responsible for about 60,000 human deaths 5U65 (ref.88); part d) antibodies (shown in cartoon representation). Heavy chains are coloured blue and annually15. A global elimination goal for light chains are coloured green. Heavy chain complementarity-determining​ region 3 (CDR H3; or human deaths from rabies has been set CDR3 in the case of the camelid antibody) for each structure is coloured orange. PG9 contains a rela- for 2030 (ref.14). The key strategies for tively long CDR H3 for human antibodies. Structures were rendered with PyMOL (version 1.8.6.0; Schrödinger LLC). achieving this goal are mass dog to break the dog–dog and dog–human transmission cycles, prompt provision of known about the relative contribution of platforms may work well in humans and postexposure prophylaxis to prevent clinical HCAbs to naturally acquired immunity to not some other species. However, within rabies among bite patients and enhanced infections and whether vaccines could be each species, individual heterogeneity in surveillance systems to detect areas where tailored to elicit immune responses focused mounting immune responses does occur, the virus circulates and targeting the rabies solely on either HCAbs or conventional and this might be due to factors such as interventions14. Whereas provision of IgG molecules. Dromedary camels are chronic underlying illnesses, genetics and rabies postexposure prophylaxis prevents susceptible to infection with a wide range age66. Performing comparative studies to clinical disease and death in people, of pathogens that are also able to infect identify the common protective mechanisms elimination of human deaths from rabies humans and domestic livestock such as across species, while accounting for is only cost-effective when combined cattle, sheep and goats; examples include individual within-species​ heterogeneity, with mass dog vaccinations69,70. Similarly, Rift Valley fever virus, Brucella species will move the field beyond identifying against brucellosis (which cause brucellosis) and Crimean– correlates of protection to defining (a bacterial zoonosis transmitted to humans Congo haemorrhagic fever (CCHF) virus63. protective mechanisms. by livestock) reduces the incidence of They are also reservoirs of Middle East human brucellosis, while improving milk respiratory syndrome coronavirus, which Vaccine deployment in different species production and other production indices emerged in 2012 and is associated with high The goals of vaccination programmes in among vaccinated livestock71. case fatality in humans63. Understanding humans and animals are similar, and include Animal vaccination against epidemic how different species are able to mount global disease eradication (permanent zoonoses is a key strategy to limit human protective immunity against common worldwide reduction of the incidence of illness. The design and implementation pathogens, despite profound differences in a specific disease to zero), elimination of vaccine programmes for this purpose IgG structures, could transform approaches of target diseases from a specified region requires interaction between veterinary to vaccine design and development. These with deliberate measures to prevent and personnel. Ideally, such differences in antibody structure can be re-establishment,​ prevention of epidemic collaboration needs to be in place before the exploited to identify different mechanisms cycles and minimization of mortality occurrence of an epidemic, rather than being of protection: for example, long CDR H3 and morbidity associated with infectious reactive72. In Kenya, the Zoonotic Disease antibodies penetrating viral glycan shields64. diseases. To date, vaccination has resulted Unit, a national entity co-led​ by medical and Importantly, a single vaccine platform can in the eradication of smallpox in humans veterinary epidemiologists for the purpose of induce protection across multiple species12, and rinderpest in cattle22,67. Although zoonotic disease surveillance, may provide including humans65, despite these differences focused on two separate species, the two an exemplar framework through which in immune response. Veterinary vaccinology eradication programmes used similar vaccine programmes to tackle endemic/ has made a substantial contribution to the vaccine deployment strategies combining epidemic zoonoses can be implemented73. broad knowledge base to develop vaccines mass vaccination campaigns to achieve herd For instance, through extant surveillance for and understand how they work, but there immunity, intensive surveillance systems to key disease syndromes in livestock, the most may be a difference in the response to identify and contain outbreaks promptly, recent Rift Valley fever outbreak in Kenya similar vaccine platforms in different and surveillance reporting and sharing of was detected in humans within a fortnight species. It may also be the case that some new knowledge that allowed eradication of confirmed livestock cases74. In such a

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scenario, Rift Valley fever vaccination could regimens and consideration of deployment manufacture (Fig. 1) mean that returns on be implemented among susceptible animals requirements very early in the investments made by vaccine developers for (licensed vaccines are already available) and development pipeline. All these factors such diseases are unlikely to be high. humans (when a vaccine is available) within influence the final cost per vaccine dose and, Initiatives such as the Coalition for a radius in proximity to the initial cases. after consideration of the potential benefit Epidemic Preparedness Innovations Such a ‘ring vaccination’ approach has its of using the product, inform go versus (CEPI) are de-risking​ the human vaccine roots in the control of disease outbreaks in no-​go decisions on vaccine implementation development process through provision of livestock75 and has been used successfully to programmes and policy. The business case funding to support early-stage​ to late-stage​ control Ebola virus disease epidemics76. for the development of vaccines against development of vaccines against epidemics, However, not all zoonoses of public many of the known zoonotic pathogens including clinical evaluation that is crucial health importance cause clinical disease in with epidemic potential is poor78. This is for licensure79. Funding schemes to advance animals. For instance, domestic ruminants largely due to the sporadic nature of the veterinary vaccine development are also such as sheep and goats are key animal epidemics they cause — for example, there available, although none exclusively targets hosts of CCHF virus, which results in are typically intervals of 5–15 years between epizootic diseases. The Global Alliance for asymptomatic infection only in these epidemics of Rift Valley fever, and there are Livestock Veterinary Medicines (GALVmed) species77. By contrast, CCHF is a highly even longer intervals between epidemics of was founded in 2004 with a primary focus fatal disease in humans and is among the CCHF and other diseases — in addition to on supporting the development and eventual diseases prioritized by the World Health their restricted geography and poor data registration of control interventions for Organization for urgent development on their economic costs, which make a wide range of livestock diseases in low- of countermeasures72. Investigating the the design of cost-effective​ vaccine income and middle-income​ countries pathophysiology and immunology of CCHF implementation plans challenging. The costs (LMICs)80; the CEPI now plays a similar virus in ruminant species may provide clues associated with vaccine development and role for human vaccines. towards identifying therapeutic targets and aid the development of vaccines against human CCHF. Furthermore, assessment Box 1 | Experience and lessons from the use of coronavirus vaccines in animals of vaccine efficacy against CCHF virus All major domestic animal species are susceptible to coronavirus (CoV) infection, typically infection in livestock field trials could resulting in clinical symptoms involving the respiratory system or the gastrointestinal system. support development of human CCHF Several licensed veterinary vaccines against CoV-associated​ disease are available (see Table 2 vaccines by providing a stringent test for for examples), and these are predominantly composed of live attenuated CoV or whole inactivated ranking the performance of candidate virions that are administered in an adjuvant. However, subunit, viral-vectored​ and other types of vaccines outside a high-containment​ recombinant vaccines are in development. Some examples of licensed animal CoV vaccines and some key immunological observations are summarized below, with further details available in laboratory environment. Due to the lack recent reviews of animal CoV vaccines89–91. of clinical disease in animals, estimation of Key observations from veterinary use of CoV vaccines89–91: vaccine efficacy following natural exposure • Virus-neutralizing​ antibodies directed to the surface spike (S) protein play a major role in could rely on serological detection of protective immunity. responses to virus components that are • The duration of vaccine-induced​ immunity is variable but can last for at least 12 months, with not part of a vaccine, thereby allowing annual boosters required to maintain protective levels of immunity. distinction of infected animals from • Vaccines can be highly protective against severe illness resulting from CoV infection yet show vaccinated animals, a concept well known limited protection against mild disease or infection. in veterinary vaccinology. Following • Passive transfer of maternal antibodies from vaccinated dams can provide protective immunity widespread COVID-19 vaccine use, a similar against both enteric and respiratory CoV infections, as has been demonstrated in cattle. serological monitoring strategy could be • T cell responses play an active role in the control of CoV infections. For instance, adoptive useful for tracking population-level​ severe transfer of CD8+ T cells from immune chickens into unvaccinated chicks provides protection acute respiratory syndrome coronavirus 2 from acute infectious bronchitis, with epitopes mapped on the nucleocapsid and spike protein. (SARS-CoV-2)​ exposure, based on • Different routes of administration can be used for CoV vaccination. Some veterinary vaccines detection of antibodies against antigens have been deployed for use orally (for example, infectious bronchitis vaccines in poultry), absent from approved vaccines. There are intranasally (for example, bovine CoV vaccines in calves) or as an oral prime followed by an several licensed veterinary vaccines intramuscular boost (for example, transmissible gastroenteritis vaccines in pigs). Induction of against coronavirus infections in domestic mucosal immunity, mediated by IgA, is thought to increase the protective efficacy of vaccines. animals (Box 1; Table 2); the experience • The emergence of CoV spike protein variants may impact vaccine performance, resulting in with licensure and use of these products insufficient protection and necessitating updates to vaccine immunogens. The strategies used provides insights into the likely performance to increase the breadth of the protective immune response against different CoV variants of vaccines against COVID-19 and other include (1) prime–boost regimens using vaccines incorporating different CoV variants (that is, coronavirus infections in humans but has vaccinating with one strain and boosting with another) and (2) inclusion of multiple CoV strains rarely been discussed in the medical debate within a single vaccine. on vaccine development. • Antibody-​dependent enhancement of CoV infection following vaccination and virus exposure can be readily demonstrated in cats. This may provide a useful model to understand the Operational considerations antibody-dependent​ enhancement phenomenon. The target product profile for any vaccine, • Monitoring of CoV antibody seroprevalence in poultry has been used to inform decisions on whether human or veterinary, needs to whether to implement a vaccination programme on the basis of the levels of flock immunity. incorporate an efficient manufacturing This is primarily aimed at achieving a cost-efficient​ disease control programme but could also be used in a scenario where vaccine supply is limited. strategy, the design of optimal vaccination

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Table 2 | Examples of licensed coronavirus vaccines for veterinary use Target CoV genus CoV-induced​ licensed product Technology Formulation species targeted by vaccine disease Cattle Betacoronavirus Gastroenteritis, Rotavec Corona Inactivated plus adjuvant Trivalent (CoV, rotavirus and neonatal calf Escherichia coli) diarrhoea Bovigen Scour Inactivated plus adjuvant Trivalent (CoV, rotavirus and E. coli) Calf-​Guard Live attenuated Bivalent (CoV and rotavirus) Poultry Gammacoronavirus Respiratory disease, Nobilis IB + ND + EDS Live attenuated Multivalent (infectious bronchitis virus, reduced egg yields Newcastle disease virus and egg drop syndrome virus) Pigs Alphacoronavirus G Gastroenteritis ProSystem TGE/Rota Live attenuated Bivalent (TGE virus and rotavirus) Dogs Alphacoronavirus G Gastroenteritis Solo-​Jec 6 Live attenuated plus Multivalent (CoV, adenovirus, inactivated plus adjuvant parainfluenza virus and parvovirus) Nobivac Canine 1-Cv​ Inactivated plus adjuvant Monovalent (CoV) Cats Alphacoronavirus G Peritonitis Felocell FIP Live attenuated Monovalent (FIP virus) CoV, coronavirus; FIP, feline infectious peritonitis; TGE, transmissible gastroenteritis.

For veterinary vaccines, the ideal cost the need for vaccination arises. However, interventions in both animal hosts and per dose for ruminants should be less this strategy would be successful only if the humans. The success of the One Health than US$0.5 to allow cost-effective​ use bulk material was stable in the long term and approach in eliminating disease burden in LMICs81. The per dose cost of human a regulatory approval strategy incorporating also requires attention to the challenges vaccines tends to be much higher and highly veterinary and human considerations was associated with eradication of zoonotic variable from product to product82. However, in place. Harmonized regulatory processes diseases in natural reservoirs. Indeed, the although higher human vaccine costs can allowing mutual recognition of vaccine elimination of the risk associated with other be tolerated, especially in high-income​ registration procedures between countries natural hosts, such as bats, rodents and countries, vaccine cost remains a key factor are already in place, aiming to address arthropods, is a long-standing​ challenge, that underlies the demand, affordability operational bottlenecks that limit rapid which may be addressed only through and implementation of access to licensed human and veterinary improved understanding of reservoir programmes in LMICs83. To further reduce vaccines84,85. species immunobiology and . deployment costs, most veterinary vaccines Research strategies and funding priorities are multivalent, composed of different Conclusions need to be realigned to improve interactions immunogens co-​formulated to target two Studying animal pathogens, diseases and between animal and human health or more diseases with a single vaccination protective immune responses has had a communities. (see Table 2 for coronavirus vaccines as an major impact on controlling human diseases George M. Warimwe 1,2,3 ✉ , Michael J. Francis 4, example). Co-administration​ of different over the past century. It is usually the case Thomas A. Bowden5, Samuel M. Thumbi6,7,8 and immunogens in a single product (for that new vaccine platforms are deployed Bryan Charleston3 example, the childhood more rapidly in veterinary species than in 1Centre for Tropical Medicine and Global Health, that targets diphtheria, tetanus, pertussis, humans. Veterinary vaccines commonly University of Oxford, Oxford, UK. hepatitis B and Haemophilus influenzae undergo rigorous safety and efficacy testing 2KEMRI–Wellcome Trust Research Programme, type b) is commonplace for the Expanded in the target hosts using challenge models Kilifi, Kenya. Programme on Immunization in children, before registration and widespread use. 3The Pirbright Institute, Woking, UK. which accounts for the bulk of global vaccine Safety testing and pharmacovigilance are 4BioVacc Consulting Ltd, Amersham, UK. use. Cross-learning​ between the veterinary especially important in food-producing​ 5Wellcome Centre for Human Genetics, Division of and medical fields from their respective animals. Also, developing cost-effective​ Structural Biology, University of Oxford, Oxford, UK. experiences relating to vaccine development manufacturing at scale is essential for 6Institute of Immunology and Infection Research, and implementation of programmes based animal vaccines. In the past few decades, University of Edinburgh, Edinburgh, UK. on multivalent or co-administered​ products the widespread use of safe and effective 7Center for Epidemiological Modelling and Analysis, could be of mutual benefit. vaccines in livestock has given confidence Institute of Tropical and Infectious Diseases, University Where a single vaccine is developed to develop the same platforms or indeed the of Nairobi, Nairobi, Kenya. for use in both animals and humans, the same active substances for use in human 8Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA, USA. same vaccine master seed stock could vaccines. However, there remain untapped ✉ be used to generate bulk material that opportunities to leverage advances in e-mail:​ [email protected] is then processed in parallel for human human and veterinary immunology for https://doi.org/10.1038/s41577-021-00567-2 Published online xx xx xxxx and animal use in accordance with the the development of vaccines, as well as respective manufacturing requirements to operational experiences to inform vaccine 1. Greenwood, B. The contribution of vaccination to global health: past, present and future. Philos. Trans. derive a livestock product and one for use deployment. Effective control of zoonotic R. Soc. Lond. B Biol. Sci. 369, 20130433 (2014). in humans from the same manufacturing infections, which account for the bulk of 2. Marsh, T. L., Yoder, J., Deboch, T., McElwain, T. F. & Palmer, G. H. Livestock vaccinations translate into run. Bulk material could be stockpiled, with public health emergencies, require One increased human capital and school attendance by downstream processing initiated as soon as Health approaches with complementary girls. Sci. Adv. 2, e1601410 (2016).

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