Following elective euthanasia at the time of predicted peak viral replication, there was no gross or histologic evidence of HeV infection in vaccinated horses; all tissues examined were negative for viral antigen by immunohistochemistry; and viral genome was not recovered from any tissue, including nasal turbinates, pharynx, and guttural pouch Table 3.
For 9 of 10 vaccinated horses, viral RNA was not detected in daily nasal, oral, or rectal swab specimens or from blood, urine, or feces samples collected before euthanasia, and virus was not reisolated from any of these clinical samples. For 1 V9 of 3 horses exposed to HeV 6 months after completing the vaccination course, low viral gene copy numbers were detected in nasal swab samples collected on postchallenge days 2—4 and 7 Figure 2 ; this finding was consistent with self-limiting local replication.
Virus was not reisolated from these samples. Scatter plot showing quantitation of the Hendra virus N gene in nasal swab samples from 1 vaccinated horse V9 and 4 control horses C1—C4 ; controls were challenged but not vaccinated. Days represent days after challenge. At the time of euthanasia, no rise in antibody titer was detected in any vaccinated horse following exposure to HeV. The formal launch of the HeV horse vaccine in November represents the culmination of multiple studies conducted in several animal infection models over the course of many years.
Studies using Nipah virus in cats 16 , 17 and monkeys 18 and HeV in ferrets 15 provided strong evidence that a HeVsG glycoprotein subunit—based vaccine could prevent not only disease but often infection in animals exposed to otherwise lethal doses of Nipah virus or HeV. Where evidence of low-level virus replication did occur in secretions, it was transient and unaccompanied by the development of clinical illness, and virus was not isolated from the secretions.
The henipavirus surface-expressed G glycoprotein has the critical role of initiating infection by binding to receptors on host cells, and antibodies directed against this protein can neutralize virus Earlier reports have shown that passive immunotherapy with antibody to the G or F glycoprotein of HeV or Nipah virus alone can prevent fulminating disease 20 : G glycoprotein—specific human monoclonal antibody prevented Nipah virus disease in ferrets 21 and HeV infection in African green monkeys 22 ; and F or G glycoprotein—specific monoclonal or polyclonal antibodies prevented HeV and Nipah virus disease in hamsters 23 — Thus it is likely that, as seen for other paramyxoviruses with a viremic infection phase e.
In the studies reported here, we show that 2 doses of a commercially formulated HeVsG glycoprotein subunit—based vaccine prevented infection in 7 of 7 horses exposed to HeV at least 21 days after the second vaccine dose; this finding is in contrast to that for unvaccinated control horses. Similar results were obtained for 2 of 3 horses exposed to HeV 6 months after vaccination.
In the third horse, which also remained clinically healthy, evidence of HeV replication was limited to low-level transient detection of viral genome but not virus from the nasal cavity. In assessing the field significance of this observation, the following must be noted: the experimental horses were exposed to considerably higher levels of HeV than have been recovered from flying foxes 1 , higher levels of viral genome were routinely found in the nasal secretions of nonimmunized horses, and all human infections have been acquired from animals in which clinical disease developed.
It is reasonable to suggest that the higher transmission risk that is clearly associated with such horses is a consequence of not only increased viral load but also of the illness itself: it is the clinically ill horse that promotes increased human—animal contact through diagnostic investigations and administration of nursing care.
We conclude that the level and pattern of virus replication in the 1 vaccinated horse do not meet the epidemiologic criteria presently associated with transmission of infection to humans. In previous henipavirus vaccine efficacy studies in cats and ferrets, a neutralizing antibody titer of 32 was shown to be protective against the development of clinical disease In the horse efficacy studies, the 3 horses with prechallenge antibody titers of 16 or 32 were similarly protected from clinical illness.
However, we caution that any correlation between antibody titer at the time of exposure to virus and levels of subsequent protection against infection and disease is unlikely to be linear; it is possible that animals with even lower titers will have epidemiologically meaningful protection against HeV exposure occurring in the field, not least because of stimulation of immunological memory.
Additional studies assessing the duration of protection are planned, and the outcome of these will further inform recommendations regarding booster vaccination. As expected, initial uptake of the HeVsG glycoprotein subunit—based vaccine was strongest in the area with the highest perceived risk for HeV infection, namely coastal Queensland, Australia.
In other regions where HeV infection of horses has not been reported, there is understandably more uncertainty regarding the value of vaccination as part of horse preventative health programs. Any reluctance to vaccinate horses against HeV that is based on assessment of risk is probably exacerbated by several factors, including the novelty of the vaccine roll-out process to the Australian horse industry, a mistaken perception that fast-tracking vaccine release involved overlooking key safety and efficacy issues, the lack of published data on safety in pregnant mares, reluctance of certain industry sectors to vaccinate because of import restrictions on HeV-seropositive horses, and cost.
Although it is likely that each of these barriers will diminish over time, our experiences may assist the development of road maps to guide the future release of vaccines against BSL-4 pathogens that are associated with highly sporadic disease events and where the decision to vaccinate is in the hands of the persons whom vaccination was designed to protect.
Several recently emerged zoonotic viruses, including HeV, Nipah, Ebola, and Marburg viruses, are classified as BSL-4 agents because of their ability to cause severe illness or death in humans and because there have been no effective vaccines or postexposure treatments to protect against the diseases they cause.
The vaccine against HeV Equivac HeV is a commercially deployed vaccine developed against a BSL-4 agent and is the only licensed treatment for henipavirus infection. Development of vaccines against BSL-4 agents for use in humans requires that the US Food and Drug Administration implement the animal rule, which requires that such vaccines first be tested for efficacy in at least 2 animal models As a veterinary vaccine, Equivac HeV did not need to meet this requirement, and it was both cheaper and faster to produce than a vaccine intended for human use.
At the same time, the vaccine is expected to provide a substantial health benefit to humans. In so doing, this vaccine encapsulates the spirit of a One Health approach, not just in terms of the interconnectedness of human and animal health but also with respect to environmental health. One consequence of the recent HeV outbreaks was a move to eradicate bat populations, despite their crucial environmental roles in pollination and reduction of the insect population.
Successful deployment of the HeV vaccine, with a targeted reduction in the risk for acute disease events in horses and humans, should help reduce the current momentum toward the setting of control policies with potential adverse effects on the environment.
Furthermore, the increasing evidence for henipaviruses and henipa-like viruses in bats in other areas 30 — 32 raises the possibility of future henipavirus outbreaks. The current HeVsG glycoprotein vaccine technology provides a platform for the rapid development of related vaccines to counter future emergent threats.
Dr Middleton, a veterinarian with a PhD in pathology, works as a senior principal research scientist. Her research interest is the pathogenesis of emerging infectious diseases including highly pathogenic avian influenza viruses, henipaviruses, severe acute respiratory syndrome, and bat-borne viruses in reservoir and spillover hosts.
Hendra virus vaccine, a One Health approach to protecting horse, human, and environmental health. Emerg Infect Dis. National Center for Biotechnology Information , U. Journal List Emerg Infect Dis v. Heine , Glenn A. Marsh , Christopher C. Broder , and Lin-Fa Wang. Author information Copyright and License information Disclaimer. Middleton, J. Pallister, R. Klein, J. Haining, R. Arkinstall, L. Frazer, J. Bingham, D. Johnson, J. White, A. Foord, H. Heine, G. Marsh, L. Wang ;. Feng, C. Huang, N.
Edwards, M. Wareing, M. Elhay, Z. Hashmi ;. Yamada ;. Corresponding author. Copyright notice. It seems simple. There is a virus, there is a vaccination, problem solved! However the logistics are far more intricate. Hendra is an emerging disease that was first identified in Australia in and since its beginnings it has been the cause of 80 known horse death fatalities, 30 of these in the last two years. What is even more scary about this virus is that it is classified as a zoonotic disease, meaning that it can be passed from animal to human and since Hendra first arose seven humans have been infected with four of them dying.
The other three have lost the majority of their functional life. Rabies, anthrax, ebola, are all names we're largely familiar with and while Hendra has not earned itself much recognition at present, it has a biology that is not yet fully understood.
The virus occurs naturally in the majority of Australian flying fox populations and is thought to be transferred to horses through contaminated flying fox urine, faeces or birthing products. The majority of humans affected were vets or vet assistants because in order to contract the disease from a horse you must be in close contact and be infected via respiratory secretions, blood, urine, saliva, and faeces.
At present there is no evidence that a human can contract the virus from another human or a flying fox. In addition to the lack of biological knowledge of this disease the symptoms of Hendra are varied and non-specific. Symptoms range from a slightly depressed appearance and high rectal temperature to colic or respiratory disease like travel sickness.
Therefore is rather identical to a lot of other common horse ailments. Also the horses experience an incubation period of up to 16 days, which means from exposure with the bat body fluid to symptoms of illness in the horse there are up to 16 days. Horses can only spread the virus from their body from 72 hours prior to the onset of symptoms through to death.
So why, during this time, would a vet wear the protective gear, if the horse is showing no signs of the Hendra virus? The good news is there is a vaccine, the bad news is the vaccine is almost as controversial as the virus itself. Equivac HeV was released late last year by the pharmaceutical company Zoetis which has manufactured a commercial vaccine based on the successful CSIRO study.
It essentially interrupts the cycle of transmission from flying foxes to horses and from horse to horse. The vaccine costs around AUS dollars for the initial two doses and 70 AUS dollars for the 6 month booster without taking into account any vet costs.
It has now been reported that some vets in Queensland will not go out to treat a horse unless vaccination can be proven, which is possible due to a microchip and national database system that enables vaccinated horses to be easily identified. Australian team vet Nathan Anthony adds that, "all equine hospitals in QLD are now restricting access of certain sick and some colic cases in unvaccinated horses and as of 1 January all of the major insurance companies have implemented a Hendra exclusion, that means that if there are delays in life saving treatment due to lack of proof of vaccination, then the policy will not pay out for mortality.
These veterinary care restrictions have led to some people accusing vets of only wanting to make money from the administration of the vaccine. Other people are scathing that some vets are overly cautious and refuse to treat horses purely because "four people have died. So why should they put their lives at risk when a vaccine is available? To gain some more understanding I talked with vet Tim Myers, who grew up in central NSW and was a practicing vet in the area for ten years.
As he is no longer practising there, he has no financial interest or political gain from the Hendra vaccine. He adds that one could never guarantee that a horse is safe from Hendra anywhere until we learn more about the disease and its transmission. At the moment one can only identify low and high risk areas. Tim agrees that the vaccine has is drawbacks, mainly that it needs to be given every 6 months by an accredited vet so this becomes costly, but adds that the side-effect, which it rarely causes, are vaccine site reactions which are "very much the same for any equine vaccine.
Tim says that as the majority of these reports involved injection site swelling and such side affects are the standard risk involved with any injection in a horse. Given the adverse event rate stands at approximately 0. Firstly the vaccine has been granted a minor—use-permit from the Australian Pesticides and Veterinary Medicines Authority APVMA to allow it to conduct widespread field trials, further establishing the safety and efficacy of the vaccine.
Under this permit the vaccine is only allowed to be administered by registered veterinary surgeons, who are required to complete an online training and accreditation package. He says he's seen good uptake of the vaccination around the Mackay region, but he won't take any risks in the future.
Dr Williams says the cost is small compared to peace of mind knowing everyone will be safe. While the virus is more common in the winter months, he says spring is a time to be aware with flowering trees and increased flying fox activity. We acknowledge Aboriginal and Torres Strait Islander peoples as the First Australians and Traditional Custodians of the lands where we live, learn, and work. Djokovic visa Follow developments from Novak Djokovic's cancelled visa in our live blog.
Of the seven people who have contracted the virus, four have died. More on:. Back to top.
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