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How we developed the Hendra virus vaccine for horses

Today we are launching Equivac® HeV, the world’s first commercially available Hendra vaccine for horses. This breakthrough is the culmination of a scientific journey that dates back to the emergence of…

Scientists worked with Hendra virus at the highest level of biosafety within CSIRO’s Australian Animal Health Laboratory. CSIRO

Today we are launching Equivac® HeV, the world’s first commercially available Hendra vaccine for horses. This breakthrough is the culmination of a scientific journey that dates back to the emergence of Hendra virus in 1994.

Although the Hendra virus “disappeared” for some ten years (with only one case reported in 1999) after it was discovered in 1994, it has recently been identified every year in Queensland with serious consequences for the health of animals and people.

For my colleagues and I working at CSIRO’s Australian Animal Health Laboratory (AAHL), in Geelong, Victoria, and overseas, these outbreaks added urgency to our research on the Hendra virus.

The initial flurry of work following the emergence of the virus led to Australian mainland flying foxes being identified as the natural reservoir host of the virus.

Research waned somewhat towards the late 1990s, when a new virus – Nipah – emerged in Peninsular Malaysia. Nipah virus was linked to outbreaks of fever and encephalitis in people, and with respiratory disease in farmed pigs.

Nipah was rapidly identified as being a close relative of the Hendra virus, and there are distinct similarities between the two. They both have the ability to lead to fatal infections in several species of animal, as well as in people. And they infect animal and human cells in a similar way.

Following the terrorist attacks on September 11, 2001, the US Congress dramatically increased the level of funding for research into countermeasures – including vaccines and antiviral drugs - for perceived potential bioterror threats, such as Nipah virus.

In collaboration with researchers of the Uniformed Services University of the Health Sciences, Maryland, we generated, in vitro, one of the Hendra and Nipah virus proteins (sG) that’s essential for infection and showed that antibodies to this protein can block virus replication.

These observations – that the G protein provoked a strong immune response in naturally occurring Hendra and Nipah virus infections, and that development of antibodies to the G protein was associated with virus clearance in infected people and animals – suggested a vaccine based on the G protein antigen may be a feasible scientific goal.

The frequency of Hendra virus incidents after 2005, particularly the Redlands outbreak of 2008 and infections at Cawarral in 2009 in which two people died following contact with infected animals, brought the desirability of a vaccine for horses more urgently into the frame.

All human infections with Hendra virus have occurred following exposure to infected horses and direct contact with their bodily fluids. We believed vaccinating horses would provide an opportunity to break the chain of virus transmission from flying foxes to horses, and then to people.

An artificially coloured electron micrograph of the Hendra virus. CSIRO/Alex Hyatt

Another benefit of a horse vaccine is that the horses themselves would be protected from a devastating infection that would otherwise most likely lead to their death.

As part of the ongoing research into countermeasures against biological threats, we’d developed the Hendra virus sG subunit vaccine with our US collaborators and tested it under laboratory conditions. The vaccine was formulated for use with an adjuvant (a substance that enhances the body’s immune response to an antigen) to enhance its efficacy.

Various forms of this preparation were evaluated in laboratory animals, where it was found to protect them from developing disease following exposure to Nipah and Hendra viruses and to prevent virus replication.

But a major hurdle to translation of this promising research into licensing for an equine vaccine was the lack of a commercial partner. This was a problem because the equine market is comparatively small, the infection problem largely confined to one state in Australia, and the public health impact of the disease is relatively insignificant compared to other illnesses.

Then, in 2010, a child received post-exposure treatment against Hendra virus infection after coming in close contact with an infected horse. This was closely followed by Queensland and Federal government funding to support the preliminary testing of the equine Hendra virus vaccine. This, in turn, acted as the catalyst for Pfizer Animal Health – our commercial partner - to join the research team.

The sG Hendra virus vaccine was soon formulated with a proprietary adjuvant suitable for use in horses. Early studies confirmed the development of immunity in vaccinated horses, prevention of disease following exposure to the virus, as well as the absence of viral shedding. This meant there was no risk of onward transmission to people or other susceptible animals.

In 2011, while this work was being undertaken, Australia witnessed an unprecedented spike in the number of Hendra virus cases in horses, in both Queensland and New South Wales. A total of 18 cases were identified. The first reported case of Hendra virus antibody detection in a dog outside of an experimental setting was also seen that year.

Intergovernmental Hendra Virus Taskforce was formed as a result, and additional funding was provided through the National Hendra Virus Research Program to ensure that the equine Hendra virus vaccine project was able to progress as rapidly as possible.

Optimising the vaccine presented additional regulatory challenges, as did undertaking efficacy studies in horses at the highest level of laboratory biocontainment. At times, progress seemed frustratingly slow. But in reality, the availability of a vaccine to protect horses from Hendra virus infection and, in turn, prevent the exposure of people to this disease, has been swift.

The Equivac® HeV vaccine is an important step towards breaking the transmission cycle of this disease, and reducing its impact on the horse-owning community. But it’s important to ensure that we continue to protect the health of our animals and people. And to do this, we need to maintain and continue undertaking research and adding to the tools in our armoury of weapons against the deadly Hendra virus.

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15 Comments sorted by

  1. David Tribe

    Senior Lecturer in Food Biotechnology and Microbiology, Agriculture and Food Systems at University of Melbourne

    Fantastic to see yet another benefit from application the tools of modern genetic technology to reduce the risks to public health, and to see Australian scientists drive tangible research outcomes.

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    1. Deborah Middleton

      Senior Veterinary Pathologist at CSIRO

      In reply to David Tribe

      Thank you for your comment; we have been somewhat fortunate in that Hendra virus infection is preventable using conventional vaccination strategy. It could so easily have not been the case.

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  2. Cath Walker

    Veterinary scientist

    Well done CSIRO! And yet again, Australian veterinarians at the forefront of cutting edge research translated into critically important and practical outcomes. Thanks Deb for the succinct outline of the process.

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  3. Catherine Oddie

    Research Development Manager

    Thanks Dr Middleton and CSIRO! The effects of Hendra have been heart breaking for the equine and veterinary communities. As a horse owner based in an area populated by flying foxes, I'm so grateful to hear about this breakthrough. It is a huge contribution to equine welfare.

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  4. Rajan Venkataraman

    Citizen

    Great news Deborah. Congratulations to you and all your colleagues who have been involved in this effort.

    I appreciate also the way you've written this article which describes the epidemiological and immunological aspects of the work as well as revealing the testing, development and commercialisation challenges.

    I had one question - do you expect that the vaccine will also be used against Nipah given that it targets a protein that is common to both Hendra and Nipah?

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    1. Deborah Middleton

      Senior Veterinary Pathologist at CSIRO

      In reply to Rajan Venkataraman

      Yes, we have shown in laboratory studies that the Hendra vaccine can protect against infection with Nipah virus. Interestingly, protection in the reverse direction (Nipah protein antigen against Hendra virus) is not so strong - which is fortunate for us here in Australia.

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  5. Luke Weston

    Physicist / electronic engineer

    I'm curious, just how do you make sure a horse will behave itself in a PC4 lab? (Talk about a potential bull in a china shop!)

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    1. Deborah Middleton

      Senior Veterinary Pathologist at CSIRO

      In reply to Luke Weston

      Actually, horse selection for this work is a major issue for us and takes place over several weeks before each project starts. Each horse is very much an individual, and we go to great lengths to get to know them beforehand and only to include animals that are temperamentally suited to the project work. In general terms, this means animals with calm personalities who enjoy interactions with people - our animal care staff spend a lot of time with the horses and we have found the horses that pass pre-selection adapt surprisingly well to the BSL4 animal facility.

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  6. Peter C. Doherty

    Laureate Professor at University of Melbourne

    Great result, and congratulations to all the AAHL team. A great example of how science works to protect humanity. Even more impressive than the (notional?) "bat cell line from Geelong" used to isolate the killer virus in "Contagion".

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  7. Suzanne Murphy

    logged in via Facebook

    My late husband, Gerry Murphy would be very pleased that your work has produced a vaccine. He was involved with the original case as Director Public Health Qld. Congratulations.

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  8. Steven Haigh

    logged in via Facebook

    Hi Deborah,

    I am very concerned in the direction that some horse organisations (particularly Equestrian NSW) that are moving towards making this vaccine compulsory for any events where horses stay at the venue overnight from 1st January 2014.

    Several countries including China, Hong Kong, Indonesia, Malaysia and the United Arab Emirates require horses to test negative to antibodies for Hendra virus. As vaccinated horses will test positive on serological tests they may be ineligible for export…

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