As future pandemics are likely to emerge from the coronavirus family of viruses and other zoonotic pathogens, an integrated approach to develop vaccines for zoonotic diseases is essential for success
by Craig Carter, Thomas Monath, Rohini Roopnarine
June 25, 2022
The COVID-19 pandemic caused by SARS-CoV-2, a zoonotic disease passed from animals to humans, from humans to humans, and humans to animals, ranks as the worst infectious disease outbreak to occur globally in over one hundred years. The Covid pandemic demonstrated once more the interconnections between human and animal health and the environment: Those interconnections, as will be shown here, cannot be ignored if success is to be achieved in addressing future pandemics.
Major international organizations, WHO, FAO, UNEP, and the OIE, have recently agreed on the following definition of One Health that highlights the interconnectivity central to the concept:
One Health is an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, and ecosystems. It recognizes the health of humans, domestic and wild animals, plants, and the wider environment (including ecosystems) are closely linked and interdependent. The approach mobilizes multiple sectors, disciplines, and communities at varying levels of society to work together to foster well-being and tackle threats to health and ecosystems while addressing the collective need for clean water, energy, and air; safe and nutritious food; taking action on climate change, and contributing to sustainable development. Source: The One Health High-Level Expert Panel
Scientific data indicate that Covid came from a SARS-like virus group that infects bats and pangolins in Asia and Southeast Asia. Globally, reported clinical cases have just tipped over 518 million cases with over 6.25 million deaths. Some news sources state that global deaths are underreported by up to 300%.
While social distancing, contact tracing, isolation, quarantining, and novel drugs have helped to curb the spread of the virus, vaccination by innovative and rapidly developed products has led to significantly reduced hospital stays and decreased mortality.
The success of vaccination has been amply demonstrated by the fact that most severe cases, hospitalizations and deaths are in unvaccinated persons.
Some areas of the world, particularly Africa and Central Asia, have low rates of vaccination. The requirement for booster doses to maintain durable immunity and protect against variant strains underscores the importance of access to efficacious vaccines as early as possible in the face of a novel zoonotic pathogen with very high transmissibility and the ability to rapidly evolve.
The COVID-19 pandemic has illustrated the ability of technology, the biopharmaceutical industry, governments and regulatory agencies to rapidly develop and approve new vaccines. However, it also uncovered the need to do better in the face of the next threats to public health from emerging pathogens, with a challenge to vaccine and regulatory science to have new countermeasures ready within one hundred days of the emergence of a new threat.
Such threats could come from animal diseases transmissible to and between humans (zoonoses), or animal diseases that do not affect humans but threaten food security, economic stability, and the environment.
One Health approach to control and prevent future pandemics
What are the best options for controlling and preventing future pandemics through vaccination?
A One Health approach offers the most logical means of developing and delivering new vaccines. One Health ensures an “all of science” approach to vaccine development in which every case benefits from cooperative efforts of veterinary and medical scientists, knowledge of the complex ecosystems that give rise to disease emergence and spread, use of animal models to test vaccine safety and efficacy, and complementary expertise in the biology of families of viruses and microbes.
To illustrate, consider the virus family Coronaviridae which contains pure veterinary pathogens of major importance (e.g. Transmissible Gastroenteritis of swine, TGE), pathogens using domesticated animals as intermediary hosts to infect humans (e.g. camels in the case of the Middle East Respiratory Syndrome, MERS), as well as SARS-CoV-2 (COVID-19) which has mainly affected humans but apparently has spilled back into animals (mink, cats, deer).
There are many examples for other virus families where the coupling of animal and human health sciences has the potential to accelerate and improve the quality of vaccine development.
There are currently four types of methods being used to develop vaccines: Whole pathogen vaccines are the legacy approaches utilizing the entire infectious organisms. alive or in a weakened (attenuated) state; subunit vaccines use only pieces of organisms that are not infectious but generate a strong immunological response; viral vectored and nucleic acid vaccines (e.g. mRNA products) possess instructions to teach human cells to develop proteins that are recognized by immune cells as not belonging in the human body, causing them to be destroyed before causing tissue and other damage.
Attention is now leaning toward using animal viruses and viral vectors for developing human vaccines, illustrating the need for connecting medical and veterinary science.
The approved vaccine against Ebola virus disease uses an animal virus (vesicular stomatitis) as a vector. A recent article that lists the most common zoonotic diseases and methods for control can be accessed here for those interested in more detail.
In 2013 a comprehensive article by Dr. Thomas Monath explored vaccines protecting against zoonotic diseases. The article describes the catastrophic global public health impact caused by zoonotic pathogens:
It is estimated that 56 different zoonotic diseases are responsible annually for 2.5 billion cases of human disease with 2.7 million deaths and substantial reductions in livestock production. Animals, including livestock and companion animals, also suffer illness and death following infection with many zoonotic infections, and livestock and poultry are subject to large-scale intentional destruction as a means of preventing human infections, resulting in huge economic losses.
It continues in advocating a One Health approach:
The purpose of this review is to stimulate the science and policy communities to seek innovative ways to interdict zoonotic diseases by integrating human and veterinary medicine and vaccine development, and by creating new streams of funding aimed at the intersection of human and animal health.
In a comprehensive review article on vaccines protecting against infectious zoonotic agents, three epidemiological frameworks are described relating to the control of zoonotic diseases via various vaccine-based interventions for diseases like West Nile Virus, Eastern Equine Encephalitis, Japanese Encephalitis, rabies, anthrax, and brucellosis.
For example, one framework comprises diseases in which wildlife transmit diseases to humans and domestic/wild animals. For this group, it may be feasible to prevent disease with vaccines for wildlife (as successfully done in the case of rabies, and in late-stage development for Lyme disease). In another framework, vaccines are developed to protect humans only. Vaccines for domesticated animals may prevent disease in these species but also prevent human infections where domesticated animals are the source of human infections (e.g. Rift Valley fever, Venezuelan equine encephalitis, or Hendra virus disease).
A unique oral vaccine that helps prevent the spread of the infectious agent that causes plague in Prairie Dog colonies may serve to reduce the likelihood of human exposure. This is similar to using oral rabies vaccination programs in wildlife to prevent infection via bites or scratches in domestic dogs and cats, thereby reducing possible exposure to human owners.
The Institute for International Cooperation in Animal Biologics at Iowa State University is a recognized collaborating center for the World Organization for Animal Health (OIE). The institute authored a seminal article that summarizes the many contributions of veterinary vaccinology to animal and human health:
Veterinary vaccines are important for animal health, animal welfare, food production, and public health. They are a cost-effective method to prevent animal disease, enhance the efficiency of food production, and reduce or prevent the transmission of zoonotic and foodborne infections to people…It would be impossible to produce enough animal protein to feed the nearly 7 billion people on earth without vaccines to prevent epizootics in food-producing animals. Without companion animal vaccines (especially rabies vaccine), many people would not keep a pet in the household and would not experience the satisfaction (author note– not to mention the significant human health benefits) of the human-animal bond. Zoonotic diseases such as brucellosis and leptospirosis would be much more prevalent without effective vaccines.
The review article authors further underscore the importance of controlling emerging and exotic animal diseases to protect human and animal health.
Increasing global travel of animals and humans is adding to the risk of pathogen transfer among species. Backyard food production (e.g., poultry, sheep, goats) is increasing, posing additional problems for disease control.
Veterinary vaccines help to reduce the utilization of antibiotics in both animals and humans, thereby mitigating risks for antibiotic resistance. Food safety vaccines such as those for E. coli O157:H7 and Salmonella enteritidis in chickens help lessen the shedding of organisms that taint products for human consumption and lessen the potential for human illness and death.
Most animal-targeted vaccines are developed to prevent infectious diseases to either improve the growth and production of food animals or to bolster the health and welfare of companion animals.
Some vaccines protect humans against acquiring dangerous zoonotic diseases from infected animals (e.g., leptospirosis). Notably, veterinary vaccines are more rapidly developed and licensed than human vaccines and at a fraction of the cost. Yet another reason to pursue a One Health approach.
The U.S. Department of Agriculture has long recognized the need for licensed vaccines to protect animals against diseases that are not endemic, not generally seen in the U.S. such as Foot & Mouth Disease (FMD) or Avian Influenza.
These diseases are known as Foreign Animal Diseases (FADs). A single outbreak of FMD in the central US would quickly cause some $200 billion in economic losses and food insecurity related to the depopulation of infected animals.
The February 2022 outbreak of Avian Influenza (H5N1 Eurasian Strain Highly Pathogenic Avian Influenza) in the US – and it is currently spreading around the world – has already led to the depopulation in America of over 30 million commercial and backyard birds in twenty-nine States with one human case reported.
If these viruses evolve (mutate) to increase transmissibility, enable person-to-person transmission, or increase mortality, the next dangerous pandemic could be set in motion.This is why the development and stockpiling of efficacious vaccines against FADs must be a high priority.
Promising future vaccines
With funding from the Coalition for Epidemic Preparedness Innovations (CEPI), Public Health Vaccines and its partner Crozet BioPharma, there has been the development of a promising vaccine against Nipah virus (NiV), which causes severe respiratory and central nervous system illness in humans with fatality rates from 40-75% (far higher than COVID-19).
Nipah was first reported in humans in Malaysia in 1999. Epidemiological investigations have revealed that human patients had a history of contact with bats, bat urine, or pigs, but person-to-person transmission also occurs.
The World Health Organization and CEPI have identified the Nipa Virus as a dangerous emerging pathogen that can cause outbreaks in areas with few medical response assets. Multiple Nipah vaccines are in development using a variety of platforms that illustrate the One Health approach: these include various animal virus vectors (VSV), poxviruses (vaccinia, canarypox), Newcastle disease virus, and rabies (ERA strain). Two vaccines are currently in clinical trials.
Some other zoonotic pathogens of concern for which vaccines are being developed are Lyme Disease, Hendra virus, Lassa virus, and Valley Fever (coccidioidomycosis).
A fascinating and innovative technology being used mostly in veterinary vaccines is known as DIVA (Differentiation of Infected and Vaccinated Animals). DIVA-enabled vaccines are becoming important tools in disease monitoring and control. A simple ELISA test can identify if an animal is infected or vaccinated. This is important for the import/export of animals. DIVA is utilized in various FMD, Classical Swine Fever, and Pseudorabies vaccines.
Another example of an area for further research and development are Universal Coronavirus Vaccines described in the New England Journal of Medicine as follows:
The past 20 years have witnessed four fatal coronavirus outbreaks… Scientific evidence and ecologic reality suggest that coronaviruses will emerge again in the future, potentially posing an existential threat.
We need a research approach that can characterize the global “coronavirus universe” in multiple species, characterize the natural history and pathogenesis of coronavirus in laboratory animals and in humans, and apply this information in developing broadly protective “universal” vaccines (protecting against all beta coronaviruses, and ideally all coronaviruses).
These words heartily suggest that to protect animals and humans from zoonotic pathogens, and for any attempt to prevent the next pandemic to be successful, we must assemble special teams of expert, energetic allied medical professionals and scientists, working together in the spirit of One Health.
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As noted above, the WHO Expert Panel (OHHLEP) definition of One Health has been endorsed by WHO, FAO, OIE and UNEP. There is a magic silver lining in the COVID-19pandemic that is striving to bring the One Health philosophy to full fruition.
This article was originally published on IMPAKTER. Read the original article.
