Hendra Virus Vaccine, a One Health Approach to Protecting Horse, Human, and Environmental Health

Deborah Middleton

, Jackie Pallister, Reuben Klein, Yan-Ru Feng, Jessica Haining, Rachel Arkinstall, Leah Frazer, Jin-An Huang, Nigel Edwards, Mark Wareing, Martin Elhay, Zia Hashmi, John Bingham, Manabu Yamada, Dayna Johnson, John White, Adam Foord, Hans G. Heine, Glenn A. Marsh, Christopher C. Broder, and Lin-Fa Wang

Author affiliations: CSIRO Australian Animal Health Laboratory, Geelong, Victoria, Australia (D. Middleton, J. Pallister, R. Klein, J. Haining, R. Arkinstall, L. Frazer, J. Bingham, D. Johnson, J. White, A. Foord, H.G. Heine, G.A. Marsh, L.-F. Wang); Uniformed Services University, Bethesda, Maryland, USA (Y.-R. Feng, C.C. Broder); Zoetis Research & Manufacturing Pty Ltd, Parkville, Victoria, Australia (J.-A. Huang, N. Edwards, M. Wareing, M. Elhay, Z. Hashmi); National Institute of Animal Health, Ibaraki, Japan (M. Yamada); Duke–NUS (Duke and the National University of Singapore) Graduate Medical School, Singapore (L.-F. Wang)

Abstract

In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease.

Hendra virus (HeV) is an emerging zoonotic paramyxovirus for which natural reservoirs are the 4 species of flying fox (Pteropus bats) found on mainland Australia (1). HeV was discovered in 1994, and since then, infections have occurred in 7 humans, 4 of whom died. Each case-patient had a strong epidemiologic connection to similarly affected horses through exposure to equine secretions late in the incubation period, during terminal illness, or at the time of postmortem examination of infected animals (2): no human case of HeV infection has been attributable to direct spillover from bats (3).

HeV infection in the bat host appears to be asymptomatic (1); however, in humans and horses there is evidence of initial virus replication in the nasopharynx that progresses through a viremic phase during which the virus spreads to major organ systems, resulting in disseminated endothelial cell infection, vasculitis, encephalitis, and pneumonia (4–7). There is no licensed anti-HeV therapeutic drug for use in any species. Experimental exposure of horses to HeV/Australia/Horse/2008/Redlands under Biosafety Level 4 (BSL-4) conditions identified comparatively low gene copy numbers in nasal secretions early in the incubation period. However, gene copy numbers increased exponentially with the onset of fever, when viral genome could also be recovered from blood, oral secretions, urine, and feces (6). Rapid progression of clinical signs, as observed in equine field cases of this disease, led to euthanasia of experimental animals on humane grounds. Viral RNA was recovered from all tissues sampled at postmortem examination, and virus was reisolated from lung, brain, lymphoid tissues, and kidney (6). In accordance with epidemiologic observations (2), it was concluded that HeV-infected horses in the immediate presymptomatic or symptomatic stages of disease pose a high risk for transmission of HeV to humans. This risk is then exacerbated because it is symptomatic horses that come to the attention of veterinarians, leading to various clinical investigations (e.g., respiratory tract endoscopy) that may facilitate human exposure to virus.

During 1994–2010, there were a total of 14 HeV outbreaks, including those with the 7 human infections. Then, in 2011, for reasons that are as yet poorly understood, an unprecedented 18 equine incidents, some involving >1 horse, occurred within a 3-month period and over an expanded geographic range, emphasizing that HeV was an unmanaged emerging disease (3). These events were accompanied by a marked rise in the number of HeV-related media reports. The reports had an increasingly politicized focus on the role (and control) of flying foxes as carriers of HeV (8) and a deemphasis of the critical role played by horses in HeV transmission to humans.

Heightened public awareness of the risk that infected horses posed to humans persisted and was paralleled by increased numbers of veterinarians leaving equine practice because of personal safety and liability concerns (9). The considerable investment in education and improved infection control measures that had been implemented did not effectively mitigate perceptions around the risks associated with the routine veterinary care of horses (10).

The actual mechanism of HeV transmission from bats to horses is probably complex and dependent upon socioeconomic, environmental, and ecologic factors (11), and there is currently no straightforward solution for preventing transmission. Eradication of flying foxes would pose extraordinary operational challenges, notwithstanding attendant moral, ethical, and environmental issues, and eliminating the interface between bats and horses is impractical for periurban and rural communities.

The most direct approach for reducing the risk posed to humans by HeV-infected horses would be implementation of a strategy that will lead to suppression of virus replication in horses. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse and human health. The emergence of several highly pathogenic zoonotic diseases in humans in recent years has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. The HeV vaccine for horses, Equivac HeV (Zoetis, Parkville, Vic., Australia), is a key example of a One Health approach to the control of human disease (12).