New vaccines needed for pathogens infecting animals and humans

Abstract

The field of “One Health” encourages researchers to collaborate across a wide range of disciplines to improve health at the animal-human-ecosystems interface. One Health recognizes the potential of emerging infectious diseases to impact public health and global food security, and the need for a multidisciplinary approach to counteract the effect of these diseases. Vaccinologists are also beginning to engage in research related to One Health, recognizing that preventing transmission of emerging infectious diseases at the animal-human interface is critically important for protecting the world population from epizootics and pandemics. In this synopsis of recent work in the One Health field, we describe some emerging One Health pathogens, discuss the importance of One Health to food safety and biodefense, propose strategies for improving One Health including the development of new vaccines and new vaccine design approaches, and close with a brief discussion of the opportunities and risks related to One Health vaccine research.

Keywords: :

• One Health
• biodefense
• emerging pathogens
• food safety
• vaccines
• zoonotic infectious diseases

Introduction

While infections due to Nipah virus might not appear to be a matter that should concern human vaccine researchers, a total of 400 human cases of fatal Nipah virus encephalitis have been reported in Southeast Asia to date, and the number of new cases per year continues to rise.¹ Nipah virus is illustrative of emerging infectious diseases that affect both humans and animals, now known as the realm of One Health. Identification and control of such infections and development of novel vaccines for these novel pathogens is the focus of this emerging field. One Health integrates the work of multiple disciplines and organizations at the local, national, and global level to improve health for people, animals, and the ecosystems by recognizing their interdependence and the potential of emerging infectious diseases to affect public health, biosecurity, and global food security (Fig. 1). One Health seeks to prevent the risks of animal-to-human transmission and diminish the effects of emerging infectious diseases by converting health science advances into effective actions and policies.

Figure 1. One Health Vaccines. Improvement of health at the human-animal-ecosystems interface.

Vaccine researchers have been slow to join One Health research efforts, which require collaboration between the disciplines of human medicine, veterinary medicine, public health and environmental sciences. Since 75% of diseases considered to be “emerging” are derived from animals,² new vaccines are needed to prevent and control these diseases, to prevent cross-species disease transmission to humans. New efforts are also required to improve our understanding of cross-species disease transmission and to develop novel diagnostic methods and to improve our understanding of the immune mechanisms of protection from disease. Considering novel approaches to accelerate the discovery of new vaccines that bridge human and animal vaccine development is both feasible and warranted.

The field of One Health includes emerging zoonotic diseases, which are new animal diseases with epizootic and pandemic potential and the capacity to infect humans. Despite significant recent advances in microbial genetics and genomics, relatively little is known about how zoonotic agents are maintained in nature or how they respond to environmental (often anthropogenic) changes. Improvements are needed in our ability to detect and respond to emerging zoonotic agents, particularly those that appear suddenly and are capable of spreading over large areas. In the next section, we describe some well-established and emerging One Health pathogens.

Emerging One Health Pathogens

H5N1

Avian influenza (AI) is a disease caused by Influenza virus A. Although AI viruses are species-specific, subtypes H5, H7, and H9 may cause sporadic infections in humans as a result of direct contact with infected birds. AI viruses consist primarily of low pathogenic strains naturally found in wild birds; however, the virus may also be found in poultry. In chickens, low pathogenic strains cause mild disease but a highly pathogenic form causes a mortality rate of 75% or greater. There have been 29 epizootics of H5 or H7 high pathogenicity avian influenza (HPAI) since 1959. The largest of these epizootics has been the H5N1 HPAI that began in China in 1996, and has since killed or resulted in culling of over 250 million poultry and wild birds in 63 countries.^3-5 Outbreaks of HPAI have had severe economic impact on the poultry industry, trade, and public health.⁶ Human cases have been reported mainly in Asia and are directly linked to outbreaks in poultry. Human infections result in a rapid onset of pneumonia and a case-mortality rate of 60%.⁷ Although some recent H5N1 cases have been reported in Egypt, Indonesia, Bangladesh, and Southeast Asia, human-to-human transmission is rare because, thus far, H5N1 has low infection and replication efficiency. However, due the likelihood of virus adaptation to a new host or reassortment with a human-adapted influenza virus there is increasing concern that the risk of human-to-human transmission will increase if the number of cases increases.^3,8

An additional concern about H5N1 is its potential reassortment with the 2009 pandemic H1N1 influenza virus, which could result in HPAI H5N1 to acquire the ability to be transmitted efficiently from an infected person to a susceptible one.⁹ H5N1 is still primarily a disease of chickens, but is considered a significant threat to humans due to its very high case-mortality rate. Fortunately, the most recent peak of H5N1 cases occurred some time ago (2007), and the number of cases has somewhat decreased in following years.¹⁰ However, H5N1 continues to circulate in poultry in highly populated countries such as Indonesia, where surveillance systems are not fully implemented. This is worrisome, since lack of control of the virus in poultry contributes to ongoing transmission to humans; indeed, there was a new case of bird to human transmission in Bengkulu Province, Indonesia, as recently as March 2012.¹¹

Hendra and Nipah virus

Hendra virus (HeV) and Nipah virus (NiV) are closely-related paramyxoviruses identified from cases of severe respiratory and encephalitic diseases in animals and humans. HeV and NiV are similar at the genomic level, but also distinct from all other paramyxovirus family members; as a result, these viruses have been classified into the new Henipavirus genus.¹² Fruit bats (flying foxes) of the genus Pteropus are the natural hosts of both viruses.¹³

Prior to the outbreak of fatal encephalitis in the Malaysian population in 1998,¹⁴ NiV was only known to circulate as a respiratory or encephalitic infection in pigs. In the last few years, several additional outbreaks of NiV have been reported in areas such as in Sarawak, Borneo Malaysia in 2000, in west Bengal, India, and in Bangladesh in both 2001 and 2004.¹⁵ The approach to controlling the NiV outbreak in Malaysia in 1998 was to depopulate all diseased and potentially infected pig farms. Approximately 11 million pigs were culled in total to control the outbreak.¹⁶ Henipavirus has also circulated in animals prior to emerging in humans. HeV was first reported in Brisbane, Australia in 1994, where it caused severe respiratory disease and death of 13 horses and one human.¹⁷ Since 1994, HeV has crossed the species barrier from the animal vector to other animals or to humans on 14 identified occasions, resulting in 40 five equine cases and seven human cases.^18,19 The HeV case fatality rate is very high – 60% in humans, and in horses it can be as high as 75%.²⁰

HeV and NiV are classified as biological safety level 4 (BSL-4) pathogens. Due to the lack of treatments for these pathogens and the severe outcome of infection, Henipaviruses are considered to be bioterrorism and agroterrorism threats. However, no commercially-produced vaccine against NiV and/or HeV is currently available. Experimental challenge studies in piglets have demonstrated that pigs may be a good animal model for testing vaccines.²¹ An ideal vaccine should cross-protect against both NiV and HeV and be safe in a wide range of species (i.e., swine, equine, canine, feline). The vaccine should also allow differentiation between infected from vaccinated animals (DIVA²²). Live vectored vaccines expressing the fusion (F) and/or attachment proteins (G) and subunit vaccines containing recombinant F and/or G proteins have been produced and shown to be safe and effective under experimental conditions.^23-25 Development of a vaccine that might work effectively to reduce transmission in animals, and also could be used to prevent infection in humans (after it is shown to be effective, safe and non-toxic) would be ideal. New approaches to designing such vaccines, using new genomics-enabled tools that are becoming available, are discussed in the last section of this review.

Rift Valley Fever

Rift Valley Fever (RVF) virus is a mosquito-borne human and animal pathogen associated with large outbreaks of severe disease throughout Africa and the Arabian Peninsula.²⁶ RVF virus is a member of the Phlebovirus genus, one of the five genera in the family Bunyaviridae. RVF has a major impact on economic stability, due to the high mortality and abortion rates in infected livestock. Human infections may occur from infected mosquito bites, through percutaneous exposure to aerosols during slaughtering of infected animals or by contact with aborted fetal materials. The spectrum of illness in humans infected with RVF can range from asymptomatic or a mild febrile syndrome, which in 2% of infected individuals can progress to more serious complications including hepatitis, encephalitis, and retinitis or a hemorrhagic syndrome with a hospitalized case fatality rate of 10 to 20%.^27-29

Outbreaks have been reported in sub-Saharan and North Africa. A major outbreak occurred in Kenya, Somalia, and Tanzania in 1997–1998 and in 2000. RVF cases were reported in Yemen and Saudi Arabia, marking the first reported occurrence of the disease outside the African continent and raising concerns that it could extend to other parts of Asia and Europe.²⁶ In late 2006 and early 2007, a RVF outbreak resulted in a total of 1,062 reported human cases and 315 deaths resulting in substantial economic losses among livestock in southern Somalia, Kenya, and northern Tanzania.³⁰

There is no commercially available RVF vaccine for humans. The US Department of Defense has an inactivated RVF human vaccine in the US, but it is only available as an experimental or “Investigational New Drug.”^31,32 Animal vaccines are available from South Africa and Egypt, but safety and efficacy needs improvement. Production of inactivated vaccines is problematic as it requires cultivation of virulent RVF virus in high level biosecurity facilities. Formalin-inactivated vaccines are currently used in endemic countries, but have several disadvantages including the use of pathogenic strains, the requirement of multiple vaccinations for immunity, and the high cost of production.³³ An attenuated vaccine strain was developed in 1949 and is still used in Africa, but it causes abortion in pregnant animals. Promising results have been reported with the mutated strain, MP12, but this candidate vaccine is not yet licensed for human or animal use.^34-37 A new veterinary vaccine, Clone 13, recently licensed in South Africa is a naturally attenuated strain that shows great promise for controlling RVF in livestock.^38,39

Foot-and-mouth disease

Foot-and-mouth disease (FMD) is not a zoonotic disease; however, it is a highly contagious livestock disease that has significant impact on the livelihood of farmers in developing countries and global food security, representing a major constraint to international trade in livestock, and animal products. FMD virus (FMDV) is a member of the Aphtovirus genus in the Picornaviridae family and is capable of rapidly infecting domestic and wild cloven-hoofed mammals, including cattle, pigs, sheep and goats, which are fundamental to the livestock industries. FMDV produces fever and soreness, excessive salivation, anorexia, reduction in milk production, and vesicular lesions that appear in the mouth and feet 48 to 72 h after infection leading to high morbidity.^40,41 Despite its low mortality rate in adult animals, millions are culled to control and eradicate this disease. FMD is endemic in many developing regions of Africa, Asia, and South America, but it has been eradicated from some parts of the world using inactivated vaccines.^42,43 However, global economic activities and travel of people and animals represent a significant risk of accidental reintroduction of FMDV. Additionally, FMDV could be used as a bioterror agent (against human food sources) due to its high infectivity.

New technologies are under research to develop effective FMD vaccines. Commercial inactivated FMD vaccines prevent clinical disease, but provide limited cross-protection against diverse serotypes. In addition, current inactivated vaccines require the removal of nonstructural proteins so that they can be used to implement DIVA test strategies.⁴⁴ Molecular vaccines for FMD are promising means to overcome the limitations of inactivated vaccines. A “dendrimeric peptide” vaccine that consists of branching T-cell epitopes and B-cell epitopes was able to induce high titers of FMDV-neutralizing antibodies, activation of T cells, and potent anti-FMDV IgA responses (systemic and mucosal). Moreover, in this particular study, the four vaccinated and challenged pigs did not develop significant clinical signs of disease whereas the control pigs all became infected, suggesting that the approach may have merit. This vaccine also inhibited local replication and airborne excretion of the virus.⁴⁵ Viral-vectored vaccine using human defective adenovirus 5 (hAd5) presents a new effective platform to deliver sequences that code for FMDV capsid proteins into animals.⁴⁶ The hAd5-FMD platform is compatible with DIVA serological tests.⁴⁷ These molecular vaccines were designed specifically for control and eradication of FMD and represent are a major step forward for the One Health movement.

Why One Health Deserves More Attention

Food safety/feeding the world’s population

In 40 y, the world population will be close to 9.5 billion.⁴⁸ Culling animals when a disease outbreak occurs is an effective but wasteful and potentially unethical means of dealing with diseases in livestock. Loss of livestock due to disease also takes a toll on the livelihoods of farmers. Food insecurity due to epidemic and emerging infectious diseases in livestock, including those cited above, deserves the attention of vaccinologists, microbiologists, and immunologists whether human or veterinary. Adopting the One Health-based approach to human health, understanding that human, animal, and environmental health are mutually dependent, and maintaining a high level of concern about any animal pathogen that may have a significant impact on human food or human health - will help protect and ensure a sustainable food supply for the coming decades. Improvements in animal vaccines will also prevent and ameliorate the burden of illness associated with foodborne threats to humans—improvements in one area will lead to improvements overall.

Biodefense

One Health also touches on biodefense, as pathogens that are considered potential biowarfare agents are easily available in settings where they occur as common animal pathogens (e.g., Anthrax). Biodefense programs aim to protect people, crops, livestock, and other living resources from pests and pathogens with the potential to cause severe economic consequences and/or public health incidents. Many of these pathogens differ in terms of their impact, but most could cause widespread disease among not only animals that are considered livestock, but also cause disease in humans. Burkolderia pseudomallei and Burkolderia mallei are examples of bioterror agents due to their exceptionally high virulence in animals and humans, and their potential for weaponization as an aerosol. H5N1 has not yet resulted in person-to-person spread, but bird-to-person spread has occurred (very few mutations are required to enable pandemic potential).⁴⁹ In contrast, FMV is considered a bioterror agent that would have a serious impact on animal sources of protein and would consequently cause major disruption if purposely disseminated. See Table 1 for a list of bioterror agents that are also One Health pathogens, such as RVF, H5N1, Henipaviruses, among others.

Table 1. Emerging diseases (and reemerging diseases)

Human	Animal
Bovine Spongiform Encephalopathy*	African Horse Sickness
Chikungunya virus	African Swine Fever
Dengue	Avian Influenza*
Ebola*	Bovine Spongiform Encephalopathy*
H5N1 Avian Influenza*	Bluetongue
Hantaan	Classical Swine Fever
HIV/AIDS	Chronic Wasting Disease
Legionaire’s disease	Food-and-Mouth Disease
Nipah virus*	Nipah and Hendra viruses*
Pandemic H1N1	Pandemic H1N1**
Rift Valley Fever*	Porcine Reproductive and Respiratory Syndrome
Severe Acute Respiratory Syndrome*	Rift Valley Fever*
West Nile*	West Nile*

Notes: *zoonoses; **Reverse zoonoses

Control of zoonotic diseases

Another important aspect of One Health is the concept of controlling a zoonotic disease at the source (in the animal reservoir) as a means of protecting people. Animal health interventions such as vaccination appear to be an effective and relatively inexpensive means of protecting public health in developing countries.⁵⁰ The quintessential example is rabies, but there are many other diseases that illustrate this, including RVF, highly pathogenic H5N1, leptospirosis, and brucellosis. In the case of RVF, millions of doses of RVF vaccines have been used in livestock during outbreaks in Africa, but due to the high level of viremia that occurs during RVF infections, serial transfer of wild type virus by needle is a recognized hazard of vaccinating livestock.⁵¹ Improved vaccines for animals that can be used prior to an outbreak are clearly needed. The control of RVF outbreaks requires limiting the circulation of virus in animals and targeted interventions for populations at risk. FAO and WHO have developed a common strategy to implement contingency plans during RVF outbreaks, and vaccination has been identified as a critical tool.⁵²

Surveillance in animals for zoonotic pathogens is critical for disease detection and control. For this reason, a well-structured international pathogen monitoring system is required. Surveillance should include not only trade animals, but also wild species since they are thought to be the source of more than 70% of all emerging infections.⁵³

The next emergent infection

One Health also plays a crucial role in public health and biodefense by taking measures against disease outbreaks caused by pathogens (e.g., bacteria, viruses, toxins) whether natural, unintentional, or intentional. Over the past 40 y, 50 new disease agents have been identified and it is most likely that new infectious diseases will appear. Microbial diversity and evolution are dynamic forces that threaten animal-human-environment health. Diverse factors may influence the emergence of new diseases; examples include, environmental changes, global travel, antibiotics overuse, population growth, human sexuality, people and animals living in close proximity, and increased human contact with wild habitats that are natural reservoirs of unknown infectious agents. One health is devoted to preventing, detecting, identifying, and responding to emerging diseases.

Strategies for Improving One Health

One Health improvement requires (1) the implementation of policies to enhance public health and global food security, such as the development of new programs and forming new partnerships to support the integration of human-animal-environment health, (2) the implementation of communication mechanisms for improved communication between health authorities and communities to prevent both disease emergence and spread, (3) the promotion and operation of One Health concept to develop an integrated strategy for response against emerging diseases, (4) the implementation of programs to train One Health-oriented professionals, (5) the design and implementation of a global surveillance system for emergent infectious diseases that gives early warning of pathogen appearance targeting specific risk areas, (6) improvement of biosecurity in smallholder and industrial farming systems to control the emergence and spread of infectious diseases, (7) a better understanding of the biology and potential impact of bioterror agents to develop countermeasures for disease control, and (8) increase control of animal disease, which may impact economies and public health.

New Vaccines for One Health

New vaccine design approaches

Veterinary vaccines to control dangerous pathogens are the most cost-effective means of controlling and eradicating diseases. However, veterinary vaccines are currently only available against a fraction of the diseases affecting animals. The desired profile for animal vaccines includes a manufacturing process that is safe under low containment conditions, and yields a large number of doses at a reasonable cost. Ideally, the vaccine would be highly efficacious with a quick onset of immunity following a single dose. One Health vaccines would ideally cross-protect against different pathogen strains, be safe in a wide range of species, be effective across all ages, and allow differentiation of infected from vaccinated animals (DIVA) testing. Vaccination should prevent virus transmission to susceptible animals and people.

Epitope-based genome-derived vaccines may be safer than vectored or attenuated live vaccines.⁵⁴ The design of these vaccines starts by selecting potential pathogen protein antigens. Sequencing technologies are able to generate genomic sequence data rapidly, which can be screened using bioinformatics tools to identify potentially antigenic genes or proteins (e.g., secreted proteins, virulent factors, and upregulated expression). Several T cell epitope prediction tools have been developed and are currently available. These prediction tools are based on large and increasing experimental database of MHC-peptide binding measurements.⁵⁵ EpiMatrix is one such tool, which has been well-validated for human vaccine development.^56-58 EpiMatrix examines overlapping 9-mer frames derived from the conserved target protein sequences and scores them for potential binding affinity against a panel of class I or class II HLA alleles; each frame-by-allele assessment that scores highly and is predicted to bind is considered to be a putative T-cell epitope. In addition to antigenicity, epitope promiscuity (i.e., epitope predicted to bind to more than one HLA allele) is a desirable trait to guarantee coverage of human population. Conservation across pathogen species variants is fundamental for heterologous protection via cell-mediated immunity.⁵⁹ ClustiMer and Conservatrix are tools that have been developed to identify promiscuous and conserved epitopes for cross-strain protection.^59,60

These new vaccine design tools permit scientists to accelerate the development of vaccines for humans. Not only do the tools map and predict vaccine epitopes directly from pathogen protein sequences, but the tools can also be used to design vaccines in silico. However, information on the immunopathogenesis of emerging infection from populations exposed to One Health pathogens is incomplete. In addition, information on animal species immune responses to One Health pathogens is extremely limited, except for those animals that serve as laboratory models for vaccine development. Information on individual species’ immune responses to T-cell epitopes derived from One Health pathogens is critically important, as this provides the raw material for developing new vaccine design tools for non-human species.

Advances in immunoinformatics tools for animals may lead to significant advances in the development of One Health diagnostics, immunology reagents, and vaccines. Buus et al. and De Groot and Martin have been applying the “pocket profile method” first described by Sturniolo et al. (refer to ref. 61) to create immunoinformatics tools for use in animal immunology studies.^62,63 The pocket profile method relies on similarities between different species MHC binding pockets, in order to create new prediction tools for MHCs from existing binding information.

New technologies are also available to develop live attenuated vaccines. Pathogen attenuation is possible by manipulating the genome to eliminate coding sequences involved in pathogenesis. The development of reverse-genetic cDNA systems enables the identification of virulence factors in pathogens’ genomes, which opens new possibilities for progress in attenuated vaccines.⁶⁴

Vaccines that include antigenic markers to allow differentiating infected from vaccinated animals (DIVA) are also under development. These vaccines facilitate monitoring of virus spread within a vaccinated population and show potential use during outbreaks. DIVA vaccines may also decrease economic loss due to commercialization restrictions with disease-free countries. Development of these vaccines is possible due to use molecular technologies and vaccine design tools.

Systems biology brings a new approach to vaccine design based upon understanding the molecular network of the immune system of two interacting systems. The massive amount of data now being generated to understand the host–pathogen interactions requires developing and validation of biologically sound models to comprehend and apply this knowledge to vaccine design. Accordingly, system biology approaches to study molecular pathway gene expression profiles of host cellular responses to pathogens holds promise as a methodology to identify, model, and predict the overall dynamics of the host–pathogen interaction. Such approach might be very useful for the rational design of both animal and human vaccines.⁶⁵

New delivery vehicles

In addition to immunoinformatics tools, new delivery vaccine vehicles have contributed to development of safer and more efficacious vaccines. These delivery vehicles maximize the exposure of vaccine antigens to the immune system and are able to target antigen presenting cell (APC) uptake.⁶⁶ New vaccines can be formulated and delivered as pseudoprotein, or as peptides in a carrier vehicle using virosomes, liposomes or virus-like particles. For instance, Inflexal (Crucell) is a virosome that incorporates the influenza virus haemagglutinin into liposomes. Gardasil (Merck and Co.) and Cervarix (GlaxoSmithKline) are licensed VLP-based vaccines against human papilloma virus (HPV). In addition, antigens or epitopes can be inserted into a viral or bacterial vector such as adenovirus or salmonella. It is also possible to design a DNA vaccine construct that encodes the antigens or epitopes identified using in silico tools and validated in vitro.^67,68 These methods for vaccine delivery are as already being used to develop vaccines for RVF and FMD.^42,52 Moreover, delivery systems based on nanoparticules and microparticles are currently under development. A number of materials can be used in these systems including polylactide co-glycolide (PlG), immunostimulating complexes (ISCoMs) (a mixture of cholesterol, phospholipids and Quillaja saponins), chitosan (a chitin-derived polyaminosaccharide), polyanhydrides, hyaluronic acids, starch, proteins, and synthetic materials such as polyethylene glycol and polystyrene.^69,70

New adjuvants

Adjuvants are also crucial as a co-stimulatory signal to drive the immune response in the right direction. Adjuvants primarily affect the innate immune response, boost the potency and longevity of antigen specific immune responses, increase immunological memory, and improve protection stimulating the appropriate type of immunity, but cause minimal toxicity. For example, adjuvants such as Alum drive the immune response toward Th2 (humoral immunity). Fine tuning adjuvants specifically for the type of immune responses desired is expected to contribute to developing more effective vaccines. Advances in the understanding of correlation of protective immunity and how innate mechanisms influence the adaptive immunity have allowed the rational design of new adjuvants such as monophosphoryl lipid A in squalene-based stable emulsion (MPL-SE).^71,72 These cutting-edge technologies are now being transferred and applied to develop veterinary vaccines.

Barriers to Improving One Health

Vaccine development for human and veterinary diseases face common technological challenges in designing a new generation of vaccines, and there are clear advantages in tackling these together. Although human vaccine research is better funded, veterinary vaccines can progress to the clinic at a much more accelerated pace because the animal model for disease is frequently also the clinical species. Moreover, large animals such as cattle can be better predictors of human immunogenicity than laboratory mice, and microbial challenge studies are more often justifiable in animals than humans.

In 2010 research funding for animal disease, their agents, and their effects was $440 million and including zoonoses research. Food safety accounted for an additional $126 million.⁷³ However, this amount is widely considered to be insufficient for the type of research that is now being performed. The new molecular and immunoinformatics approaches also require the development of specific reagents (for quantifying and phenotyping immune response), which are generally not available. One Health vaccine research deserves greater support and more attention, since it is closely connected to human health and well being as well as to food security and safety. Moreover, One Health vaccine research improves bioterrorism and agroterrorism readiness, by developing treatments and controls for non-zoonotic diseases. The field has been defined, the need has been described and now it is time for animal and human vaccine experts to begin to collaborate to improve health at the animal-human-ecosystems interface. The kinds of emerging infections to be addressed in the context of One Health do not respect species boundaries, and thus it is to our collective advantage to cooperate so as to protect the public, ensure global food security, and counteract the destructive effect of epizootic and pandemic threats.

Abbreviations:
AI	=	avian influenza
APC	=	antigen presenting cell
BSL-4	=	biological safety level 4
DIVA	=	differentiating infected from vaccinated animals
FMD	=	foot-and-mouth disease
FMDV	=	foot-and-mouth disease virus
FAO	=	Food and Agriculture Organization of the United Nations
hAd5	=	human defective adenovirus 5
HeV	=	hendra virus
HLA	=	human leukocyte antigen
HPAI	=	high pathogenicity avian influenza
HPV	=	human papilloma virus
ISCoMs	=	immunostimulating complexes
MHC	=	major histocompability complex
MPL-SE	=	monophosphoryl lipid A in squalene-based stable emulsion
NiV	=	nipah virus
PlG	=	polylactide co-glycolide
RVF	=	rift valley fever
WHO	=	World Health Organization

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.