Strengthening One Health Through Investments in Agricultural Preparedness

Abstract

There are links among agriculture and zoonotic diseases, transboundary diseases in domesticated and wild animals, climate patterns, and human population migrations. A natural or intentionally occurring high-consequence infectious disease (“biothreat”) often has no geographic boundaries and has the potential to result in disease epidemics in humans, animals, or both. Although significant strides have been made globally in preparing for a natural or intentional introduction of an emerging and/or zoonotic disease, much remains to be accomplished. Enhancing animal health and well-being is a vital component to enable a sustainable, safe, and nutritious food supply for global food economies. This article explores the biothreat environment, its One Health interrelationship, and the significance and role of US agriculture in One Health. We provide an overview of the US Emergency Medical Countermeasure Enterprise (EMCE) and current state of veterinary and zoonotic medical countermeasures portfolio management in the US government, veterinary biologic industry, not-for-profit groups, and public-private partnerships. The highest zoonotic and epizootic threats to the US livestock industry are briefly reviewed, and currently available veterinary medical countermeasures are presented. Lastly, important gaps and priorities are identified, followed by specific recommendations to address these gaps.

The inextricable links among agriculture and transboundary animal and zoonotic diseases, domesticated and wild animals, climate patterns, and human population migrations can be traced back to as early as the mid-14th century. Wheat, gerbils, and wet springs followed by warm summers may have coalesced to unleash the Black Death bubonic plague pandemic that resulted in 50 million deaths across the eastern hemisphere and had a devastating impact on the global economy.¹ Fast forward 700 years to 2015, when Mayaro virus, a little-known arbovirus in the Togaviridiae family, first discovered 6 decades earlier in Trinidad forest workers,² was diagnosed for the first time in young Haitian patients that live above the 18 parallel north.³ Although it is too early to know for certain, similar anthropogenic drivers behind the bubonic plague pandemic may still be at work today. Climate change–driven arthropod distribution, migratory bird patterns, and food shortages, coupled with civil society disruption following the 2010 Haitian earthquake, may have acted synergistically to advance Mayaro virus, an emerging alphavirus found in the tropical rainforests of Central and South America, north by more than 500 miles and within striking distance of the US mainland.

Biothreat Environment

Biothreat is defined here as any natural or intentionally occurring high-consequence infectious disease. Biothreats often have no geographic boundaries, can be natural or man-made, and inflict disease on humans, animals, and, in many cases, both. As exemplified by the 2016 response to Zika virus outbreaks in the Americas, the US preparedness level against a natural, off the radar epidemic or pandemic is lacking. The fact that 10% of the FY2017 health security–related budget was dedicated to pandemic influenza and emerging infectious disease programs underscores a critical gap and lack of commitment to addressing this vulnerability.⁴

Although we have made significant strides in preparing for a natural or intentional introduction of a zoonotic disease globally, there still remains much to be accomplished. The Global Health Security Agenda (GHSA) has worked to build capacity and evaluate response capabilities globally. Joint External Evaluations (JEEs), which are a part of the GHSA, have helped identify areas for improvement and areas of strength. Likewise, the World Organization of Animal Health (OIE) Proficiency of Veterinary Services (PVS) program has also helped countries identify and improve areas of preparedness for disease response through strengthening their veterinary services capacities.⁵

However, global preparedness for a bioterrorist attack or global pandemic, which could kill more humans and animals than a nuclear attack,⁶ still lacks coordination and resource commitment globally. One has only to look at global history to understand how devastating and realistic a bioterrorist event can be. For example, in the 14th century BCE, the Hittite army used rams infected with Francisella tularensis to kill their Arzawan enemies.⁷ This historical event unleashed a long-lasting human epidemic of tularemia that is widely believed to represent the earliest known record of biological warfare. Moreover, the first incidence of bioterrorism against the US homeland may have occurred more than 250 years ago, when British officers distributed smallpox-laden blankets and handkerchiefs to Odawa Native Americans.

Today, our nation is far better prepared to withstand a bioterrorist attack compared to 700 years ago when the Hittites attacked the Arzawa kingdom. However, the biothreat environment is rapidly increasing in complexity, and improved efforts for preparedness are needed, particularly at the human-animal interface. The 2017 National Defense Authorization Act (NDAA) contains a key provision that calls out a critical recommendation of the bipartisan Blue Ribbon Study Panel on Biodefense—namely, establishment of a comprehensive national biodefense strategy and implementation plan.⁸ Efforts by the current administration toward developing a national biodefense strategy should strongly consider incorporating agriculture emerging infectious disease threats, in addition to human-focused threats.

One Health Interrelationship

The One Health concept and its principles are rooted in the earliest known records of food animal domestication, namely Mesopotamian pigs (Sus scrofa domesticus) around 13,000 BCE.⁹ It may not be simply coincidence that domestic swine were shown to be the first established link between animal and human infectious disease. In the mid-19th century, the German physician Rudolf Virchow coined the term zoonosis while studying a swine roundworm, Trichinella spiralis.¹⁰ His findings contributed to the birth of public health and the first government-mandated meat inspections at food processing plants. It is also noteworthy that only 12 months following its formation in 1946, the Centers for Disease Control and Prevention (CDC) created a Veterinary Public Health Division with a mission to protect and improve both animal and human health.¹¹

Although there is no universally accepted definition of One Health, there is an urgent need to transform the archaic US policies and paradigms of separately funded national public, animal, and environmental health programs. Biothreats must not continue to be addressed solely in the context of human health. Animal health and food security are linked to public health, and control of animal emerging infectious diseases is paramount for managing the risks and consequences associated with accelerating environmental changes and unparalleled global human population growth.

Role of US Agriculture in One Health

Domestic animal food production is critical to global food security. It has been estimated that animal diseases reduce food animal production by more than 20% worldwide.¹² There is a need to significantly increase animal protein output to feed the more than 9 billion people projected to inhabit the world by 2050.¹³ At present, livestock and primarily small ruminants support the livelihood of almost 1 billion of the world's poorest people living in developing countries. In many of these communities and societies, veterinary disease surveillance, diagnosis, and treatment is lacking or nonexistent. Consistent with the “One World, One Health” concept, more than 100 countries have adopted a coordinated medical and veterinary health policy document, prepared by the World Health Organization (WHO), the United Nations Food and Agriculture Organization (FAO), and the OIE.¹⁴ This document encompasses zoonotic and foodborne diseases and recognizes the urgent need to control dangerous pathogens at their source, in animals, to help mitigate public health problems. Enhancing animal health and well-being is a vital component of supporting a sustainable, safe, and nutritious global food supply.

The indispensable contribution of the US agricultural sector, and specifically animal agriculture, to the overall national economy must be brought to the forefront in every One Health discussion. The US agriculture enterprise is a $1 trillion business, employs approximately 11% of American workers, and is deemed a US critical infrastructure.^15,16 Natural and malicious biothreats can disrupt the daily operations and productivity of the agriculture enterprise and lead to significant impacts on our food supply, Americans' livelihoods, the economy, and public health. The important role that livestock protein serves in One Health has been overlooked for far too long. Broadened federal interagency coordination and engagement and resources for emerging infectious disease activities that address both human and animal health are needed to safeguard the nation's food supply. The fact that approximately 49.4% of FY2016 biodefense funding was allocated to the Department of Health and Human Services (HHS), while slightly less than 0.05% was assigned to the US Department of Agriculture (USDA), is evidence of this need.⁴ Furthermore, the Strategic National Stockpile (SNS) has been appropriated between $500 million and $625 million each year between 2004 and 2016,¹⁷ whereas the USDA National Veterinary Stockpile (NVS), which was created under HSPD-9,¹⁸ is currently budgeted to receive $4 million in FY2018.¹⁹

These are just 2 of numerous examples that highlight the funding disparity between animal and public health, and the lack of equitable resources to support a One Health strategy and implementation plan. Increasing domestic agricultural R&D budgets would support more One Health interactions between agencies and allow for greater international collaborations that would help support a more informed preparedness and response capability. Food security is national security, and it is integral to public health.²⁰

At the international level, the potential for food insecurity to result in societal disruption is evident in the case of Syria, where a 2006 drought drove widespread migration of unemployed farmers to urban centers, which is thought to have contributed to that country's civil war.²¹ In the case of Yemen, tropical cyclones disrupted food production in 2015, further worsening conditions for civilians already suffering in that country's civil war.²²

A panel of agrodefense experts at the Blue Ribbon Study Panel of Biodefense 2017 workshop, held at Kansas State University, discussed the challenges of and potential solutions to protecting the nation's multifaceted agriculture industry from natural or intentional biothreat incursions. In October 2017, the panel released their findings from their consideration of the threats to US agriculture in “Special Focus: Defense of Animal Agriculture.”²³ In this report, the panel acknowledges the threats posed by emerging, reemerging, and zoonotic diseases, along with the potential for agroterrorism to affect domestic agriculture.²³ The panel offers a number of recommendations intended to address vulnerabilities of US agriculture, such as increased investment in the NVS and associated countermeasure development (eg, vaccines and rapid diagnostics), establishing a vaccine bank for foot-and-mouth disease virus (FMDV), and ensuring that the National Biodefense Strategy (presently under development) and its implementation plan include a focus on threats affecting food and agriculture.²³

Emergency Medical Countermeasure Enterprise

Phemce

Since the Project BioShield Act of 2004 and its 2013 reauthorization,^24,25 there has been a multi-billion-dollar investment in the Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) to enhance biothreat and emerging infectious disease preparedness from a strictly human medical countermeasure (MCM) perspective. The PHEMCE mission is primarily coordinated in the HHS enterprise's public health (CDC), regulatory (Food and Drug Administration, FDA), and translational research (National Institute of Allergy and Infectious Diseases, NIAID) mission partners. PHEMCE also cooperates with several interagency partners, including the Department of Defense (DoD), the Department of Homeland Security (DHS), and the USDA. Because PHEMCE was primarily established to address public health biothreats, efforts against animal and agricultural threats have been very limited.

Barda

Within PHEMCE and HHS, the Biomedical Advanced Research and Development Authority (BARDA), which was created in 2006 under the Pandemic and All-Hazards Preparedness Act,²⁶ serves a catalytic role by providing an integrated, systematic approach to developing and manufacturing needed MCMs (eg, diagnostics, drugs, therapeutics, vaccines) against a broad spectrum of public health threats, which are subsequently procured through Project BioShield funding for the SNS. BARDA supports critical functions in the PHEMCE chemical, biological, radiological, and nuclear (CBRN) MCM process. Whereas DHS serves to identify and assess threats, BARDA evaluates the potential medical and public health consequences of those threats.

The HHS Office of the Assistant Secretary for Preparedness and Response (ASPR) and the Office of Policy and Planning (OPP) define requirements for MCMs, and then the National Institutes of Health (NIH), BARDA, and the CDC execute strategy and implementation plans for MCM development and acquisition.²⁷ Threat foci in the BARDA CBRN portfolio include programs to facilitate the development of MCMs for infectious/biological agents such as anthrax, smallpox, botulinum toxin, and Ebola.²⁸ BARDA has facilitated late-stage development and acquisition of a number of MCMs, including a vaccine and antitoxins for anthrax, a botulinum antitoxin, and a smallpox vaccine for use by immunocompromised individuals.²⁹ In the past decade, Project BioShield and BARDA have made notable achievements in public health preparedness and response, including building a pipeline of more than 80 candidate countermeasures, procuring and stockpiling 21 SNS countermeasures, and achieving FDA approval for 6 of those MCMs for CBRN-associated indications.³⁰

Despite these successes, the Blue Ribbon Study Panel on Biodefense 2015 bipartisan report, “A National Blueprint for Biodefense: Major Reform Needed to Optimize Efforts,” coincidentally released at the end of the largest Ebola epidemic in humans ever documented, listed a set of recommendations to address gaps in biodefense preparedness.³¹ Notably, 5 of the 33 recommendations incorporated an animal health/zoonotic disease/One Health component. Twelve months later, this same panel issued a report titled “Biodefense Indicators: One Year Later, Events Outpacing Federal Efforts to Defend the Nation.”³² Of the 46 short-term action items listed, 96% had either no or only partial action taken.

BARDA's Influenza Division was initially launched with a mission for MCM advanced development and procurement for human H5N1 pandemic influenza preparedness and response. The H1N1 influenza pandemic in 2009, which evolved from North American and Eurasian swine influenza lineage gene swapping, underscores the fact that pandemics are unpredictable and can originate from diverse animal species.³³ For example, the natural incursion of H5N2 highly pathogenic avian influenza (HPAI) in US midwestern poultry flocks in the spring of 2015 resulted in the destruction of almost 50 million birds in 15 states, with total economic losses estimated at $3.3 billion.³⁴ A follow-up investigation demonstrated that HPAI virus aerosolization around infected premises was a significant risk factor for HPAI spread.³⁵ This finding suggests that an H5N1 or H7N9 HPAI outbreak in the US poultry industry might pose a major threat to public health if these influenza strains acquire the ability to be readily transmitted from birds to humans and from humans to humans.

Despite this stark warning, BARDA's influenza and other 3 divisions have remained complacent with respect to the opportunities and challenges that are evident for addressing MCM production through a One Health approach. In addition, the federal government remains focused on public health MCMs versus strengthening and institutionalizing a One Health approach for combating emerging infectious diseases.

Veterinary and Zoonotic Disease MCM R&D

The absence of a unified, comprehensive, and coordinated strategic plan among the multitude of federal agencies active in the transboundary and emerging and zoonotic disease (defined herein as any zoonosis that is recently recognized or newly evolved, or has increased in incidence or expanded into new geographical, host, or vector range) R&D space underscores the critical need for a centralized governance body. There are presently 6 federal agencies—USDA, DoD, HHS, DHS, Department of the Interior (DOI), and the US Agency for International Development (USAID)—that separately fund and manage transboundary, emerging, and zoonotic disease countermeasure programs. The following nonexhaustive list presents an overview of major agency programs relevant to this domain.

US Department of Agriculture

Since 1954, the USDA's primary investments in transboundary animal disease programs have been executed at the Plum Island Animal Disease Center (PIADC). The USDA Agricultural Research Service (ARS) Foreign Animal Disease Research Unit (FADRU) conducts basic and applied research on high-priority livestock transboundary animal diseases, primarily foot-and-mouth disease, African swine fever (ASF), and classical swine fever (CSF).³⁶ Historically, less than half of 1% of the ARS annual budget is spent on transboundary animal disease research; only $4 million was recommended in the FY2018 president's proposed budget.

The USDA Animal Plant Health Inspection Service (APHIS) Veterinary Services Foreign Animal Disease Diagnostic Laboratory (FADDL), also located at Plum Island, is devoted to transboundary animal disease diagnosis and is responsible for managing the North American Foot-and-Mouth Disease Vaccine Bank (NAFMVB).³⁷ FADDL has diagnostic capabilities for more than 30 foreign animal diseases and serves as both an OIE and an FAO reference center. FADDL is also responsible for the training and proficiency test program for the National Animal Health Laboratory Network (NAHLN)³⁸ and provides hands-on training to state, federal, and foreign veterinarians in foreign animal disease clinical and laboratory diagnosis. The FY2018 president's proposed budget for FADDL was $3.4 million, which represented 0.4% of the APHIS total discretionary budget.

The USDA ARS Arthropod-Borne Animal Diseases Research Unit (ABADRU), part of the Grain and Animal Health Research (CGAHR) in Manhattan, Kansas, conducts basic and applied studies on arthropod-transmitted viral diseases of domestic animals.³⁹ Arbovirus pathogens currently under study include African swine fever virus, Rift Valley fever virus (RVFV), and exotic bluetongue.

The USDA ARS Southeast Poultry Research Laboratory (SEPRL), located in Athens, Georgia, hosts a research program focused on exotic and emerging poultry diseases, such as avian influenza.⁴⁰ As part of coordinated USDA efforts associated with avian influenza, SEPRL coordinates with public health authorities to assess the zoonotic potential for influenza viral strains.

Lastly, the National Institute of Food and Agriculture (NIFA) functions as the extramural science funding agency in the USDA's Research, Education, and Economics mission area.⁴¹ Their priority science areas in food security, food safety, and climate variability and change contribute to science policy decision making associated with One Health and agricultural preparedness. NIFA serves an important complementary role in transboundary animal disease research through its extramurally funded programs in research, extension, and education. In FY2016, NIFA sponsored and funded 16 projects related to transboundary animal diseases and emerging infectious diseases.⁴²

Department of Defense

Both the Army and Navy operate emerging infectious disease and zoonotic laboratory networks that are primarily associated with countermeasure R&D and disease surveillance. There are several active zoonotic disease R&D programs at the US Army Medical Research Institute of Infectious Diseases (USAMRIID, Frederick, MD), including but not limited to Rift Valley fever, Venezuelan equine encephalitis (VEE), Burkholderia mallei (glanders), Yersinia pestis, and Crimean-Congo hemorrhagic fever (CCHF).

Disease surveillance programs operate under the Global Emerging Infections Surveillance and Response System (GEIS).⁴³ Created in 1997 under Presidential Decision Directive NSTC-7,⁴⁴ GEIS provides centralized coordination, technical and funding support for emerging infectious disease surveillance, R&D, outbreak response, and local (overseas) capacity-building efforts. The Defense Threat Reduction Agency's Cooperative Biological Engagement Program (CBEP) also funds biothreat capacity building with international partner countries and operates programs associated with biosecurity, biosurveillance, and biothreat response to emerging and zoonotic diseases.⁴⁵

Department of Health and Human Services

In addition to BARDA, as previously discussed, HHS maintains multiple institutes, centers, and programs that are relevant to biodefense and are therefore relevant to any discussion of transboundary, emerging, and zoonotic diseases with regard to their potential impact on public health.

As an NIH institute, NIAID maintains a broad basic and applied research portfolio that supports the treatment and prevention of infectious diseases. NIAID's FY2017 budget for biodefense was $1,739 million and addressed a comprehensive list of biodefense and emerging infectious disease priority pathogens.^46,47 Most of this funding is targeted to countermeasure development for public health activities, and little if any of these funds support emerging and zoonotic disease research in livestock. In addition, modeling efforts for determining spread of a livestock disease to the human population or vice versa have not been supported. DHS and CDC periodically review and provide input into this list from both threat assessment and emergency response perspectives. Category A pathogens pose the greatest risk to public health and national security, and among the 17 pathogens on this list, 12 are known zoonotic agents. The fact that 12 of the 17 Category A priority pathogens—agents that pose the greatest risk to public health and national security—are zoonotic is consistent with the observation that approximately 70% of all infectious diseases originated from animals.⁴⁸

In addition to its previously discussed role as part of the PHEMCE, the CDC performs many functions relevant to transboundary, emerging, and zoonotic diseases. In conjunction with USDA APHIS, the CDC operates the Federal Select Agent Program, which provides oversight for the use of biological select agents and toxins.⁴⁹ In addition, CDC programs carry out basic and applied research involving highest-consequence infectious diseases, many of which are zoonotic. For example, the Viral Special Pathogens Branch (VSPB) conducts studies on pathogens such as Ebola virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, and other emerging viruses of public health importance.⁵⁰ In addition, the Division of Vector-Borne Diseases (DVBD), located in Fort Collins, CO, performs research on vector-borne viruses and bacteria, many of which are zoonotic (eg, Japanese encephalitis and eastern equine encephalitis viruses).⁵¹

DHS Science and Technology

In response to HSPD-9, and in alignment with the transfer of ownership of PIADC from the USDA to DHS,⁵² DHS Science and Technology (S&T) established an Agricultural Defense Branch in the Chemical-Biological Division and in FY2005 initiated a Foreign Animal Disease (FAD) Vaccines and Diagnostics Countermeasures program. Primarily executed through the Target Advanced Development Branch at Plum Island, the program mainly focuses on next-generation foot-and-mouth disease vaccines and diagnostics and the identification of an effective African swine fever DIVA (differentiating infected from vaccinated animals) recombinant subunit vaccine. Key accomplishments to date for this program include the first-ever licensed foot-and-mouth disease recombinant vaccine⁵³ based on a viral-vectored platform currently being used for PHECME biodefense targets,⁵⁴ and the first licensed foot-and-mouth disease serology diagnostic assay that is manufactured in the United States.⁵⁵ These 2 countermeasure tools can be used in a vaccinate-to-live foot-and-mouth disease outbreak response strategy.

The program previously funded a One Health vaccine project for Rift Valley fever through interagency agreements with USDA ARS and DoD/USAMRIID, and it also funded evaluation of a Nipah virus vaccine candidate for swine. In addition, DHS S&T and the Office of National Laboratories (ONL) is presently funding the construction of the National Bio- and AgroDefense Facility (NBAF), a “state-of-the-art biocontainment facility for the study of diseases that threaten both America's animal agricultural industry as well as public health.”⁵⁶ The facility is estimated to cost $1.25 billion to construct, and it will serve as a national interagency and international resource, offering capabilities for research, veterinary countermeasure development, disease diagnosis, and training. The NBAF is envisioned to be an enhanced replacement for PIADC. Specifically, NBAF will provide the first US large animal biosafety level-4 (ABSL-4-agriculture) facility, in order to house cattle and other large livestock that will be used in studies of highly pathogenic BSL-4 zoonotic agents.

This new ABSL-4 facility will be capable of supporting much needed research and countermeasure development in the highest containment facility available. This capability is currently lacking in the United States. The NBAF is intended to function as a continuation and expansion of the PIADC interagency model, wherein DHS serves as the facility owner and maintains a targeted advanced development scientific program, while USDA partner programs (ARS and APHIS) maintain their respective basic research and confirmatory diagnostic and training missions, respectively. The NBAF will also house a Biologics Development Module (BDM) that will provide small-scale production of standardized biological reagents needed for basic and translational research, and biological test materials for supporting proof-of-concept studies and early-phase veterinary countermeasure development.

To date, funding to operationalize and stand up a robust vaccine and diagnostic countermeasure R&D program has not been allocated for this facility, nor has the funding been committed to equip and operate the facility. If a successful transition from the PIADC to NBAF is to occur, it is imperative that Congress act to allocate stable, multi-year funding that will support a robust transition and ultimately an expanded research and diagnostic mission in the new facility. The NBAF facility will be a critical node for US One Health national and international activities and, as such, will need robust operational and R&D budgets to engage with public health agencies in collaborative, multidisciplinary research.

DOI/US Geological Survey National Wildlife Center

The US Geological Survey National Wildlife Center's mission is “national leadership to safeguard wildlife and ecosystem health through dynamic partnerships and exceptional science.”⁵⁷ The NWHC has several wildlife emerging infectious disease biosurveillance programs in which avian species may serve as reservoirs or amplifying hosts, including highly pathogenic avian influenza and West Nile virus. A notable example of a One Health project is the NWHC's work on a wildlife vaccine against sylvatic plague. Cutting-edge technology combining unmanned aerial vehicles and peanut butter–laced viral-vectored oral vaccine pellets are being used by the US Fish and Wildlife Service to vaccinate prairie dogs against sylvatic plague to protect and save the endangered black-footed ferret population.⁵⁸

Transboundary, emerging, and zoonotic infectious disease programs have historically been underfunded. The fact that 5 diverse and separate cabinet-level agencies have transboundary and emerging infectious disease–related programs serves to reinforce silos and weakens the One Health concept. A more innovative and integrated strategy for addressing catastrophic animal or zoonotic disease outbreaks in the US agriculture system is critically needed. The recommendations presented at the end of this article are a first step in this direction.

Veterinary Biologics Industry

The vast majority of developed countries (eg, the United States, Canada, the EU states, Japan, Australia) are listed as free from transboundary animal diseases by the OIE. Practically speaking, this translates into the absence of a profitable market for transboundary animal disease vaccines in these wealthier countries. Assessment of the net present value (ie, the difference between the present value of cash inflows and cash outflows to analyze profit of any investment) that drives for-profit veterinary vaccine investment decisions in these developed country markets fails to justify internal R&D funding for transboundary animal disease vaccine programs. Despite this roadblock, the major global players in the veterinary biologics industry do develop and sell transboundary animal disease vaccines in developing country markets, including South America, the Middle East, and Southeast Asia.

Zoetis

Although not a major global player in the transboundary animal disease vaccine market, Zoetis has developed a small but impressive transboundary animal disease vaccine portfolio. In 2012, the company (formerly Pfizer Animal Health) was the first to develop and license a Hendra virus vaccine for horses in Australia. A year later, the USDA Center for Veterinary Biologics (CVB) issued Zoetis a conditional license for a live, attenuated Rift Valley fever cattle vaccine, the first such vaccine ever licensed in the United States.⁵⁹ Under a public-private partnership co-funded by the 6th and 7th EU Framework Programs, Zoetis developed and received a European Medicines Agency license for a novel live, DIVA vaccine for classical swine fever in 2015. Zoetis was subsequently awarded 2 USDA contracts to supply the USDA APHIS National Veterinary Stockpile with classical swine fever vaccine for deployment in the event of a future outbreak of the disease in the US domestic swine herd. In 2016, Zoetis received a USDA conditional license for an avian H5N1 vaccine and was awarded a contract to supply the NVS with more than 60 million doses of vaccine. In 2015, with a lack of veterinary vaccines available, an H5N1 outbreak in poultry flocks in the Midwest resulted in the death or culling of more than 49 million birds and is considered to be the largest animal health emergency in the United States in modern history. Total economic losses were estimated at $3 billion.³⁴ Zoetis has also collaborated with Transboundary Animal Biologics, Inc. (TABI), under a DHS S&T–funded research project, to evaluate a Nipah virus vaccine candidate in swine.⁶⁰

Boehringer-Ingelheim

Boehringer-Ingelheim entered the transboundary animal disease vaccine space following the company's recent acquisition of Merial from parent company Sanofi, and it is now one of the top manufacturers of foot-and-mouth disease vaccines. Historically, Merial's veterinary public health division has been a strong advocate for foot-and-mouth disease vaccine banks,⁶¹ and Merial has maintained active collaborations with DHS S&T and USDA ARS at Plum Island over the past several years to further develop and seek additional product licenses using the adenovirus-vectored foot-and-mouth disease vaccine platform. In addition, Boehringer-Ingelheim holds product licenses for 2 H5-based avian influenza vaccines, as well as a classical swine fever vaccine.

Merck Animal Health

Merck Animal Health is committed to One Health, as recently evidenced by a company-authored publication that demonstrates that canine rabies vaccination is a cost-effective method in support of a public health policy to prevent human exposure and infection.⁶² It is not a great leap to suggest that a recently described MERS-CoV and rabies combination vaccine candidate would serve as an excellent exemplar of a human and canine One Health vaccine.⁶³ Merck Animal Health is the global leader in foot-and-mouth disease vaccine production, and it also produces and markets a classical swine fever vaccine. The company recently acquired Harrisvaccines, a US veterinary biologics company that has been collaborating with DHS S&T PIADC on the potential application of their RNA particle vaccine platform for next-generation foot-and-mouth disease and classical swine fever vaccines. The acquisition opens up the possibility of a rapid response strategy to quickly develop, under APHIS VS Memo 800.213 guidelines,⁶⁴ numerous foot-and-mouth disease vaccines for novel, emerging strains against which current vaccines have been shown to be largely ineffective.⁶⁵

Eli Lilly

Although Eli Lilly (Elanco) does not have a transboundary animal disease vaccine portfolio, the company maintains strong corporate stewardship in food security and the human-animal bond.⁶⁶ The company has active partnerships with Heifer International and the Enough Movement, a global community initiative to address the most significant issues that contribute to food insecurity.⁶⁷ The company's recent acquisition of Boehringer-Ingelheim VetMedica's US feline, canine, and rabies vaccines portfolio demonstrates the company's growing commitment to the global animal health business.

Bayer Animal Health

Bayer Animal Health was the first to license a classical swine fever recombinant subunit vaccine based on an insect cell vaccine platform and is one of the leaders in foot-and-mouth disease vaccine production. Despite the absence of a robust transboundary animal disease vaccine portfolio, Bayer Animal Health has demonstrated a corporate commitment and responsibility associated with One Health.⁶⁸

Not-for-Profit and Public-Private Partnerships

These entities not only serve a critical role in promoting One Health through the enhancement of animal health and well-being, but they also serve as an important funding source for the research and development of veterinary vaccines for emerging infectious diseases and zoonotic diseases endemic or epizootic in sub-Saharan Africa and Asia.

EcoHealth Alliance

This global environment health–focused nonprofit is leading the research effort to protect wildlife and public health from emerging infectious diseases and pandemics. The company maintains active, progressive programs in biosurveillance, One Health, and pandemic prevention. One of their most recent biosurveillance studies identified numerous regions throughout the world with the highest number of unknown viruses with spill-over potential for human infection and which animals are most likely to carry the viruses.⁶⁹ EcoHealth Alliance is actively involved in filling knowledge gaps associated with filovirus (eg, Ebola, Marburg) distribution and transmission, and it is the leading nonprofit calling for improved global biosurveillance strategies to combat the emergence of highly virulent emerging infectious diseases. Through a funded project from the USAID PREDICT program,⁷⁰ EcoHealth Alliance filled a critical knowledge gap in the global diversity of coronaviruses, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS-CoV), and their geographical location in various animal hosts.⁷¹

GALVmed (Global Alliance for Livestock Veterinary Medicines)

This UK-based nonprofit, often working with donor funding from other nonprofits such as the Bill and Melinda Gates Foundation and Wellcome Trust, is the global leader in addressing the most economically important smallholder livestock infectious diseases. GALVmed has an extensive network of partners in academia, public research institutes, and the veterinary biologics industry. Using a product development partnership approach, in parallel with market development activities, GALVmed is helping to identify and co-develop a comprehensive portfolio of licensed vaccine products for the smallholder livestock communities in Africa and Asia. GALVmed is currently managing several veterinary emerging and zoonotic infectious disease programs, including African swine fever, peste des petits ruminants, Rift Valley fever, and brucellosis.

CEPI

The Coalition for Epidemic Preparedness Innovations (CEPI) is the most recently launched and most ambitious public, private, philanthropic, and civil organization consortium associated with emerging infectious diseases and One Health.⁷² Founded in January 2017 by the Norwegian government, Wellcome Trust, the Bill and Melinda Gates Foundation, and the World Economic Forum, CEPI aims to address and solve the major barriers to epidemic vaccine development through a proactive accelerated vaccine development strategy. CEPI uses an innovative approach to identify and build vaccine technology rapid response platforms and institutional capacities to enable rapid deployment against emerging infectious diseases and unknown biothreats. CEPI's scientific advisory committee has selected 3 zoonotic diseases from the WHO list of priority pathogens—MERS, Lassa, and Nipah—as initial targets.⁷³

Bill and Melinda Gates Foundation

In addition to funding support to GALVmed for veterinary diseases of small ruminants and to CEPI for emerging zoonotic diseases, the Gates Foundation established the Collaboration for TB Vaccine Discovery (CTVD) to implement a revised tuberculosis vaccine strategy.⁷⁴ Relevant to the One Health and agricultural resilience concept presented herein, the revised strategy includes the identification of improved animal models. Interestingly, a recent publication highlighting the synergies between human and bovine tuberculosis research approaches suggests that bovine TB models could serve as a useful tool to screen human TB vaccine candidates.⁷⁵

Rockefeller Foundation

Established over 100 years ago, the Rockefeller Foundation is recognized for having had a significant impact on public health and tropical disease discovery through field work and surveillance.⁷⁶ For nearly 2 decades, the Rockefeller Foundation has supported early detection of zoonotic diseases through effective disease surveillance networks. In 2007, they launched the Disease Surveillance Networks (DSN) initiative, which strengthens capacity-building efforts for disease detection, monitoring, and prevention.⁷⁷ Their involvement (along with the Gates Foundation) in the Connecting Organizations for Regional Disease Surveillance (CORDS) initiative has strengthened the effectiveness of global response systems. The CORDS project has worked to build bridges among the numerous disease surveillance networks that are associated with several international agencies.⁷⁸

Overview of Highest Threat Diseases

It is estimated that 60% of existing human infectious diseases are zoonotic, 75% of emerging human infectious diseases have an animal origin, and 80% of biothreats are zoonotic pathogens.⁷⁹ Lessons learned and gained from the recent widespread West Africa Ebola virus epidemic (2014-2016) prompted the WHO to issue in May 2016 “An R&D Blueprint for Action to Prevent Epidemics.”⁸⁰ This strategic preparedness and action plan is designed to implement R&D paradigms to improve One Health responses to future outbreaks and epidemics. Importantly, most, if not all, of the 10 priority viral diseases listed are zoonotic pathogens and/or have an animal host(s) as part of the virus life cycle.

A useful new database, DISCONTOOLS, ranked the most important epizootic and zoonotic diseases, using 6 criteria: disease knowledge, impact on animal health and welfare, impact on public health, impact on wider society, impact on trade, and control tools. It identified research gaps that need to be addressed to more adequately prepare for and control an outbreak.⁸¹ Among the 52 infectious diseases that were ranked, the top 10 include 6 zoonotic diseases and 3 epizootic livestock diseases. The livestock diseases are considered to be transboundary animal diseases by the OIE. The specific pathogens listed and briefly summarized below were derived from the DISCONTOOL list of the top zoonotic (Nipah virus) and top 4 epizootic (peste des petits ruminants, African swine fever, Rift Valley fever, and foot-and-mouth disease) diseases. This list is nonexhaustive, and the chosen pathogens are presented as exemplars reflective of the range of characteristics of prioritized transboundary and zoonotic diseases.

Nipah Virus

Nipah virus is the highest-ranked zoonotic disease on the DISCONTOOLS list and also appears as one of the top-priority diseases on the most recent WHO list.^80,81 Nipah virus is a relatively new emerging zoonotic pathogen in the Paramyxoviridae family that first surfaced in 1998-99 in northern Malaysia, in a region that was experiencing expansion of swine production into the tropical rainforest. Pigs were identified as the immediate spill-over hosts during the initial outbreak, which resulted in 105 human deaths and the culling of more than 1 million pigs.⁸² It was subsequently shown that anthropogenic events associated with widespread slash-and-burn tropical rainforest destruction, and subsequent haze and drought leading to photosynthesis cessation of flowering and fruit trees, led to widespread migration of Nipah virus–carrying fruit bats to new areas where the swine piggeries were co-located with cultivated orchards.⁸³ This is an excellent case study of the animal-human-environmental interface associated with disease emergence, and this incident served as the reference case on which the movie Contagion is loosely based.

The more recent identification of Nipah-like henipaviruses in African bats and serological evidence of their spillover into human populations in Africa,⁸⁴ coupled with the lack of a licensed veterinary or human Nipah virus vaccine, has many One Health scientists concerned over the potential for new henipavirus outbreaks in other African bat ecosystems. Several very promising Nipah virus human vaccine candidates have been identified, but very few have been evaluated for safety and efficacy in swine challenge models.

Peste des Petits Ruminants

Often called ovine rinderpest or goat plague, peste des petits ruminants (PPR) is caused by a contagious, often lethal morbillivirus in the Paramyxoviridae family. Peste des petits ruminants affects domestic small ruminants (eg, goats, sheep), and its geographic range has been expanding in recent years. PPR is endemic across sub-Saharan Africa, and outbreaks as far south as Zambia have been reported. It is also endemic throughout the Middle East and South Asia and is spreading into China. PPR is considered by the United Nations Food and Agriculture Organization (FAO) to be the number one threat to food security in the developing world. With many similarities to bovine rinderpest, the first animal infectious disease declared globally eradicated in 2011 through a vaccination campaign lasting 25 years, peste des petits ruminants is now the focus of a global eradication program being led by the OIE and FAO.⁸⁵ Unfortunately, although several good PPR licensed vaccines exist for disease outbreak control, none possess the product profile required for achieving global eradication. Specifically, PPR thermostable vaccines with DIVA capability need to be developed.

A notable example of the power of a private-public partnership to address and solve this problem is the Bioscience eastern and central Africa—International Livestock Research Institute (BecA-ILRI Hub).⁸⁶ The hub unites more than 40 international development institutions (eg, World Bank, Africa Development Bank, USAID, FAO, OIE), technical research partners, and nongovernmental organizations. In partnership with the African Union—Interafrican Bureau for Animal Resources (AU-IBAR), the BecA-ILRI Hub recently developed a peste des petits ruminants lyophilized vaccine prototype formulation that is stable at ambient temperatures. The Botswana Vaccine Institute is currently manufacturing pilot lots, and the AU-Pan African Veterinary Vaccine Center will serve a coordinating role in the final product production, quality assurance, and dissemination for field studies.

African Swine Fever

Traditionally called “pig plague,” African swine fever is the number one global threat to domestic swine. African swine fever virus, the only member of the Asfaviridae family, is highly contagious and causes an often lethal, acute viral hemorrhagic disease. Largely confined to the African continent since it was first described in Kenya over 100 years ago, African swine fever reemerged from sub-Saharan Africa in 2007 following its accidental introduction into the Caucasus region.⁸⁷ The disease has spread into the southern, central, and eastern Russian Federation, causing epizootic outbreaks primarily in wild boars but also occasionally in domestic pig populations. Recent incursions of African swine fever into the European Union, combined with the lack of an effective vaccine, have the global pork industry on high alert. The accidental introduction of porcine endemic diarrhea virus (PEDV) into the United States from China in 2013 and its rapid spread throughout the US swine production system exposed the vulnerabilities of the economically important US pork industry to the incursion of transboundary animal diseases.⁸⁸ In 2013, USDA ARS coordinated the formation of the Global African Swine Fever Alliance (GARA),⁸⁹ an international consortium of 32 partners, 6 collaborators, and 7 stakeholder institutions (including several veterinary biologics companies) to share research experiences, collaborate, and develop countermeasures to prevent and control the spread of African swine fever.

Rift Valley Fever

The second highest ranked zoonotic disease on the DISCONTOOLS list, Rift Valley fever also appears on the WHO priority disease list for 2018. Rift Valley fever is caused by a phlebovirus in the Bunyaviridiae family and was first described in Kenya in 1931 during an epidemic among sheep. Rift Valley fever is also on the global move as evidenced by the first documented outbreak outside the African continent in the Arabian peninsula in 2000.⁹⁰ Rift Valley fever outbreaks in humans are almost always preceded by abortion storms in pregnant sheep and cattle and high mortality in young livestock (eg, lambs, calves) that serve as intermediate, amplifying hosts.⁹¹ Rift Valley fever transmission-competent mosquitos (Diptera: Culicidae) species have been identified in North America, raising US One Health concerns.^92,93 Rift Valley fever and Zika outbreak scenarios in the United States have been modeled based on the US experience with West Nile virus (WNV), which also has its roots in the Rift Valley region of Africa. West Nile virus rapidly spread across the United States following its introduction in 1999. Rift Valley fever is an excellent example of a zoonotic disease for which there are relevant sheep and marmoset models for One Health Rift Valley fever vaccine countermeasure development.⁹⁴ Based on safety and efficacy results in cattle and sheep, a recently USDA licensed Rift Valley fever veterinary vaccine could be easily fast tracked by FDA for human approval.

Foot-and-Mouth Disease

Foot-and-mouth disease is the most highly transmissible virus disease of cloven-hoofed animals. Foot-and-mouth disease virus is an RNA apthovirus in the Picornaviridae family. Foot-and-mouth disease is endemic or epizootic in more than 100 countries worldwide, including most of Africa and throughout the Middle East and Asia. It is an OIE reportable disease, and countries where it appears are restricted in economic trade of livestock and livestock products.

Although eradicated from the United States in 1929, foot-and-mouth disease is considered the number one biothreat to the US livestock industry (eg, cattle, swine, sheep, goats) because of the potential severity and magnitude of an outbreak. For example, the authors of a Kansas State University study predicted that the costs associated with a foot-and-mouth disease outbreak that was restricted to the midwestern United States could result in $188 billion in losses to the livestock and allied industries and up to $11 billion in losses to the US government.⁹⁵ Concerns surrounding a potential foot-and-mouth disease outbreak led the USDA APHIS to develop an FMD Foreign Animal Disease Preparedness and Response Plan (FAD PreP)⁹⁶ and supported the DHS Science & Technology Directorate's establishment of a DHS Agriculture Branch in the Chemical-Biological Division (CBD). The DHS CBD Agricultural Branch was tasked with funding and coordinating a transboundary animal disease vaccine countermeasure development program, primarily focused on next-generation foot-and-mouth disease vaccines that can be safely manufactured and stockpiled on the US mainland.

Concern over a foot-and-mouth disease catastrophic outbreak in the United States is underscored by the recent livestock industry stakeholder testimony to the House Agriculture Livestock and Foreign Agriculture Subcommittee in support of allocating $150 million in the 2018 Farm Bill for a foot-and-mouth disease vaccine bank,⁶³ representing an approximately 38-fold increase over the $4 million allocated in FY2017. In 2010, USDA ARS assumed coordination of the Global Foot-and-Mouth Research Alliance (GFRA)⁹⁷ to develop sustainable global partnerships in support of strategic goals to successfully prevent, control, and eradicate foot-and-mouth disease. Annual research reports and gap analyses are generated and shared with all partners, collaborators, and stakeholders.

The diverse nature of the aforementioned pathogens underscores the need to recognize that there is no singular approach to disease control. Indeed, agricultural preparedness requires a range of tools, beyond vaccines and diagnostics. A spectrum of factors must be considered when evaluating investment in MCM for agriculture. Pathogen-specific aspects, such as the natural history of the pathogen, host range, involvement of vectors and wildlife, carrier state, and susceptibility of agricultural species must be assessed.

In addition, broader consideration of topics such as the feasibility of available control options, prevailing control policies (eg, depopulation or vaccinate-to-live or to-slaughter), environmental impact, and the role of agricultural production practices must also occur. The science for countermeasure development is rapidly outpacing policy and, as such, has created a void in the US government commitment to purchase, stockpile, and use newly developed countermeasures in the event of a widespread transboundary animal disease outbreak.

Available Medical Countermeasures

Project BioShield executes contract awards for CBRN products deemed by DHS material threat assessments to pose a material threat against the US population. Among the 13 currently listed agents, 11 are viral or bacterial pathogens and 9 of these are zoonotic.⁹⁸

The SNS serves as the nation's main repository of pharmaceuticals, vaccines, and medical supplies for deployment in the event of a public health emergency.⁹⁹ The FY2017 budget for the SNS is $575 million. This multibillion-dollar formulary is coordinated through PHEMCE, which periodically determines which countermeasures and response tools to stockpile based on ongoing threat assessments conducted by DHS. The only currently stockpiled vaccines are for smallpox and anthrax. Notably, there are no veterinary-specific pathogens on the PHEMCE material threat list, and thus there are no veterinary vaccines in the SNS.

Under HSPD-9 issued in 2004, USDA APHIS has the responsibility for maintaining a national veterinary stockpile (NVS).¹⁸ NVS's goal is to deploy, within 24 hours of a disease outbreak, approved (licensed) countermeasures against the transboundary animal diseases of highest economic consequence, including HPAI, foot-and-mouth disease, exotic Newcastle disease, and classical swine fever. Since the NVS is precluded from funding transboundary animal disease vaccine R&D, and its annual budget is approximately only 0.7% ($4 million) of the SNS budget, there is virtually no market incentive for veterinary biologic companies to invest shareholder dollars in next-generation transboundary animal disease vaccine development and product licensure that hopefully will never have to be deployed in the United States. As previously mentioned, the NVS has issued relatively small contract awards for procurement of limited amounts of classical swine fever and HPAI vaccines that were already licensed.

Our nation's preparedness against a natural or intentional outbreak of foot-and-mouth disease relies on the North American Foot-and-Mouth Disease Vaccine Bank (NAFMDVB), a regional vaccine bank created in 1982 by the United States, Mexico, and Canada. There are limited quantities of foot-and-mouth disease serotype-specific vaccine available that fall short of the surge capacity needed to address any event beyond a very limited, focal outbreak.¹⁰⁰ A moderate foot-and-mouth disease outbreak in highly livestock-dense areas at the regional level would quickly outpace even the global supply of foot-and-mouth disease vaccine in emergency reserves.

Historically, the NAFMDVB annual budget has been less than one-half of 1% of the annual SNS budget. Although global foot-and-mouth disease vaccine manufacturers provide FMD vaccine antigen concentrate to the NAFMDVB under contract, there are no market incentives to produce or provide ready-to-deploy finished vaccines. To this end, there have been renewed calls to modernize the NAFMDVB and provide appropriate funding to help protect the $100 billion a year (cash receipts) livestock industry.

Earlier this year, both the National Cattlemen's Beef Association and the National Pork Producers Council testified to the House Agriculture Livestock and Foreign Agriculture Subcommittee to support funding $150 million per year over the next 5 years for a new foot-and-mouth disease vaccine bank.¹⁰¹ These and other livestock industry groups have requested that the 2018 Farm Bill address this urgent issue. Although this request will address the foot-and-mouth disease vaccine bank, it is a much too limited, myopic reaction to the perceived single highest biothreat to US agriculture. It still would leave the nation without a comprehensive approach and funding for addressing the many other high-consequence livestock and zoonotic disease pathogens and threats.

The minimal amount of investment by the veterinary biologic industry in transboundary animal disease vaccine R&D has been primarily funded through a DHS S&T Agricultural Defense contract. Merial (now part of Boehringer-Ingelheim Vetmedica), Harrisvaccines (now part of Merck Animal Health), Benchmark Biolabs, Bavarian-Nordic, Novavax, and Kentucky BioProcessing have been the previous recipients of and collaborators with the DHS S&T Agricultural Defense transboundary animal disease vaccine program. The termination of the DHS S&T Agricultural Defense program, first reflected in the FY2018 president's proposed budget and reinforced in the FY2019 president's budget, in which it is proposed that the operational responsibility for the NBAF be transferred from DHS to USDA,¹⁰² will end a program intended specifically to advance current transboundary animal disease vaccine candidates through the “valley of death” phase of development.

As mentioned previously, there are only a handful of animal health companies manufacturing vaccines for classical swine fever and HPAI for limited markets outside of the United States. There is only marginal investment by the private sector to identify and develop a safe, effective African swine fever vaccine. Similarly, none of the major veterinary biologic companies are actively investing in next-generation vaccines for foot-and-mouth disease or peste des petits ruminants or for zoonotic diseases such as Rift Valley fever or Nipah virus.

There remains an important need to incentivize veterinary biological companies to invest R&D funding in agricultural defense through a USDA APHIS sustained commitment to expand the National Veterinary Stockpile through contract awards for the purchase of countermeasures against the highest threats to agriculture.

Gaps and Requirements

As highlighted above, according to the Blue Ribbon Study Panel report issued in December 2016, 96% of the short-term recommendations listed in the Blue Ribbon Study Panel on Biodefense 2015 bipartisan report had no or only partial action taken.³¹ In the context of the report and this article, several of the most important gaps and unmet needs identified are: (1) integrating animal health and One Health approaches into biodefense strategies, (2) improving surveillance of and planning for animal and zoonotic outbreaks, and (3) prioritizing innovation over incrementalism in MCM development (which includes establishment of an antigen bank for human and animal biothreats). Additional, significant gaps and unmet needs of note in the 2016 report are: (4) unifying biodefense spending, and (5) reforming BARDA contracting. Lastly, specific unmet needs associated with the theme of this article include: (6) modernizing and expanding the foot-and-mouth disease vaccine bank, (7) updating 9 CFR 102.6 to allow for rapid response development of transboundary animal disease vaccines for use in emergency animal and zoonotic disease outbreaks, (8) establishing public-private partnerships with the veterinary biologics industry to undertake transboundary animal disease vaccine R&D, and (9) leveraging current PHEMCE and DoD supported Centers for Innovation in Advanced Development and Manufacturing (CIADMs) and MCM Advanced Development Manufacturing (ADM) facilities, respectively, for emergency production of transboundary animal disease vaccines.

Recommendations and Conclusions

Based on the information presented and the 9 gaps and unmet needs listed above, the following recommendations are offered, some of which align with those of the 2017 Blue Ribbon Study Panel Agriculture Report “Special Focus: Defense of Animal Agriculture”:

1. Establish a dedicated Veterinary Health Emergency Countermeasure Enterprise (VHEMCE).

VHEMCE would coordinate federal interagency collaboration and lead in the development of strategic and implementation plans to promote and pursue veterinary medical countermeasures to strengthen One Health and protect the nation's agricultural infrastructure against the highest priority transboundary, emerging, and zoonotic disease threats. VHEMCE strategic goals could include: (1) incentivizing the development of veterinary countermeasures for economically catastrophic transboundary animal diseases; (2) developing, manufacturing, and procuring medical countermeasures to high-priority zoonotic pathogens dependent on animals as amplifying or reservoir hosts; (3) creating new USDA regulatory processes and incentives to foster veterinary countermeasure development; and (4) developing rapid response logistical and operational plans for veterinary countermeasure deployment in concentrated animal feeding operations.

One important distinction of veterinary countermeasures from human countermeasures is the challenge and often requisite capability to be safe and effective in more than one domestic animal species, as well as in wildlife animal species that can serve as spillover or immediate host reservoirs. VHEMCE's primary focus should be on the biothreats and vulnerabilities of the US national livestock herd (ie, cattle, swine, sheep, goat) and poultry flocks (ie, chickens, turkeys), as these are the agricultural industries of highest economic, food security, and One Health concern.

2. Enact and expand funding for the Securing Our Agriculture and Food Act, signed into law by the president on June 30, 2017.¹⁰³

This will increase agricultural resilience by authorizing and funding the role of DHS to coordinate agroterrorism preparedness programs, including improved animal and zoonotic disease surveillance in the United States. The authors assert that establishing the VHEMCE is more important than deciding on its siting among the interagency environment, which may be contentious. One option, in order to align with this act, is for the VHEMCE to reside in and be coordinated by the newly established DHS Countering Weapons of Mass Destruction (CWMD) office, which will serve to “elevate and streamline DHS efforts to prevent terrorists and other national security threat actors from using harmful agents, [including biological materials] … to harm Americans and U.S. interests.”¹⁰⁴

Alternatively, the VHEMCE could be sited in and be coordinated by the USDA Office of the Chief Scientist (OCS), who is charged with a coordinating role for research conducted by the department, in addition to coordinating linkages between the department and “other science-performing organizations in government (U.S. and abroad), academia, and industry.”¹⁰⁵ The mission of the OCS is well-suited to align with the VHEMCE, as that office could coordinate intra-agency collaboration with USDA among ARS, APHIS, and NIFA; interagency coordination with other One Health performers, such as DHS and HHS; and also facilitate engagement with nonfederal parties such as academia, industry, and nonprofit and international entities.

3. Leverage rapid response, pathogen-agnostic vaccine platforms currently under development for human MCMs toward transboundary animal disease vaccine development.

This would address the innovation over incrementalism gap and enable the establishment of a deep and broad antigen bank for both human and animal biothreats. A unified One Health national stockpile would enable deployment and use co-strategies for zoonotic and veterinary medical countermeasures.

4. Enact the Biodefense Strategy Act of 2016 (S.B. 2967).¹⁰⁶

This bill aims to execute a unified national biodefense strategy that aligns all the federal agencies and programs working in the biodefense space. The bill calls for a comprehensive national strategy and a dedicated biodefense budget that would be administered by a single federal leader. This biodefense enterprise would incorporate both human biodefense and agriculture animal defense. While a single focus point for biodefense is optimal, the federal government should ensure that the veterinary and animal health component is equally represented alongside this leader at the highest levels.

5. Enact legislation to revise the Pandemic and All Hazards Preparedness Act (PAHPA, Public Law No. 109-147)²⁶ to establish a Veterinary Advanced Research and Development Authority (VARDA).

Use the BARDA blueprint and its demonstrated strengths, but incorporate lessons learned from the current challenges associated with BARDA contracting. Working closely with DHS and USDA, VARDA could define and prioritize veterinary health countermeasure requirements and harmonize and focus current disparate transboundary animal disease research and development activities. VARDA should have contract authority and could serve as the actionable agency to provide a unified, standardized approach to the development and purchase of biologic and diagnostic tools for veterinary emergencies. Legislative revision should be used to provide multi-year appropriations for VARDA and enable a refocusing on One Health domestic initiatives. VARDA should be tightly aligned with BARDA and actualize a unified national biodefense strategy that incorporates both human and livestock biodefense.

6. Enact a 2018 Farm Bill that incorporates subject matter expert and livestock industry stakeholder recommendations associated with multi-year funding of a new foot-and-mouth disease vaccine bank.

This paradigm shift would incentivize the major global veterinary biologic companies to invest in the development of next generation foot-and-mouth disease vaccines that can be safely manufactured in the United States. The DHS S&T PIADC Targeted Advanced Development group has funded the development of adenovirus vectored foot-and-mouth disease vaccine master seed virus for numerous different foot-and-mouth disease serotypes/subtypes. In the possible absence of continued funding by DHS S&T or new funding by the private sector, none of these candidates will be developed into licensed vaccines. In addition, at least one RNA-based rapid response platform for foot-and-mouth disease has successfully completed the prototype demonstration stage. Funding in the 2018 Farm Bill would enable further development of this and other rapid response platforms for foot-and-mouth disease. While this is a start in enhancing preparedness for foot-and-mouth disease, there remains much to be done to ensure we are prepared for additional livestock, emerging, and zoonotic disease threats.

7. Issue a new USDA APHIS VS memorandum that is consistent with 9 CFR 102.6 but allows for rapid response development of transboundary animal disease vaccines for use in emergency animal and zoonotic disease outbreaks.

The new memorandum should incorporate key elements of VS Memorandum 800.213 that currently support veterinary vaccine platforms.

8. Support public-private partnerships with the veterinary biologics industry, academia, public research institutes, and international agencies to undertake foot-and-mouth disease and animal emerging infectious disease vaccine R&D.

These partnerships could be modeled after or integrated with current programs being managed by GALVmed or in the future by CEPI.

9. Allow PHEMCE- and DoD-supported CIADMs and ADMs to manufacture veterinary vaccines for transboundary animal diseases and emerging infectious diseases for antigen bank stockpiling and emergency response and recovery activities under USDA APHIS jurisdiction.

Veterinary biologics industry manufacturing facilities typically operate at or near full capacity for livestock and poultry endemic disease vaccine production. None of the CIADMs or ADMs are currently operating close to full capacity. Access to these facilities for veterinary vaccine production would increase manufacturing bandwidth for veterinary vaccine production for antigen banks and emergency response. The ADMs and CIADMS could periodically produce veterinary vaccines to demonstrate capability, and the vaccine serials could enter into the national antigen bank repository.

Imagine a scenario in which the zoonotic bacterium Pasteurella multocida, responsible for the 2015 mass die-off of approximately 250,000 saiga antelopes in less than 1 month in the remote steppes of central Kazakhstan,¹⁰⁷ occurred in an intensive swine or poultry operation within a short distance from a Midwest or East Coast major population center in the United States. This script is more plausible than one might first contemplate. This potent toxin-producing zoonotic bacterium causes atrophic rhinitis in young pigs and fowl cholera in commercial poultry flocks, 2 veterinary species responsible for the spillover of Nipah virus and influenza H7N9, respectively, into humans.

The next unforeseen or simmering zoonotic pathogen enemy is lurking and waiting for the opportunity to expeditiously amplify through a US concentrated domestic or wildlife animal population proximal to a highly concentrated human population center and explode into a human epidemic or pandemic. The time to maximize national preparedness to respond to veterinary and zoonotic threats is now. Strengthening One Health through agricultural resilience is a race against time.

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