The Hendra virus is a potent pathogen transmitted to humans from animals that cause a severe and often fatal illness in both infected horses and humans. Originating from fruit bats, the virus caused an outbreak in Australia in 1994.
Now, a team of research experts from the Hendra Virus Taskforce and the University of Queensland’s Australian Institute for Bioengineering and Nanotechnology conducted the world’s first human clinical trial to determine the efficacy of the Hendra antibody trial. In the phase, I clinical trial, the treatment was safe and able to neutralize the viruses.
Published in the journal The Lancet Infectious Diseases, the study involved 40 healthy participants. The promising results of the trial will pave the way for further trials, which will involve infected patients. The Hendra antibody developed was a monoclonal antibody, which is a laboratory-produced molecule that’s carefully engineered to attach to particular defects in targeted cells, in this case, a Hendra virus cell.
A process developed by University of Queensland researchers to produce larger quantities of the Hendra virus therapeutic antibody could be expanded to manufacture treatments for other potentially deadly viruses around the world.
Henipaviruses and fatality risk
The Hendra virus and Nipah virus are closely related to RNA henipaviruses, which were first discovered in 1994 and 1998, respectively. These henipaviruses are noted to originate from flying foxes, a type of fruit bat, which serve as natural reservoir hosts for the viruses. The viruses cause illnesses with high mortality of 57 percent, with seven cases of Hendra virus in Australia. The Nipah virus has caused 373 deaths in the south and southeast Asia from 1998 to 2018.
Though there is a small number of outbreaks and cases, these viruses were classified by the World Health Organization (WHO) as diseases with epidemic potential that should be the focus of research. There is little known research about these viruses, and they can trigger outbreaks in the future. Further, the Nipah virus has the ability to mutate at a fast rate, making human-to-human transmission possible. They may cause global outbreaks and as early as now, finding an effective treatment is crucial.
“Given the high death rate from infection by henipaviruses, their ability to cause infection in multiple organs including the brain, and their unique ability to spread to humans from bats via a wide range of animal species including horses and dogs, doctors need a safe way to neutralize them,” Dr. Elliott Geoffrey Playford from Princess Alexandra Hospital, Australia, said in a statement.
"Our results are the first to confirm that administering an antibody that binds to the virus is safe, making it the most promising therapeutic option to date for addressing this unmet medical need,” he added.
Therapeutic antibody efficacy
The therapeutic antibody, called the m102.4, was developed by Professor Chris Broder and his team. It works by blocking the virus’s entry to healthy human cells, activating the immune system to combat it.
The m102.4 has shown to successfully neutralize henipaviruses in previous experiments in non-human subjects. It works by binding to proteins on the surface of viruses that would typically allow the virus to conquer host cells and trigger an infection.
In the current study, the team wanted to assess the safety of the antibody in humans and to see what happens to it as it travels through the body. They found that the m102.4 doses used in the study were safe and well-tolerated by healthy participants. There were no serious or adverse effects and in blood tests, the team found that the antibody remained active for at least eight days after administration.
“When there's a possible case of henipavirus infection or people suspect they might have been exposed to one of the viruses, there often isn't time to confirm a diagnosis before it could become too late to do anything about it," Dr. Heidi Carroll from Queensland Health, Australia, said.
"Based on the results of our trial, we suggest offering a single dose of 20mg/kg of m102.4 to people likely to have been exposed to one of the viruses, or two doses separated by 48 hours to patients with clinical signs of infection,” she added.
The production of the Hendra virus therapeutic antibody could be expanded to make the treatment for the deadly virus in larger scales. The ability to produce these antibodies, combined with formal regulatory green light as a result of promising clinical trials, will play a huge role in addressing the impact and spread of these diseases.
What is the Hendra virus?
The Hendra virus causes respiratory and neurological disease in both horses and humans, while its natural reservoir is fruit bats, the Centers for Disease Control and Prevention (CDC) reports.
The transmission is through exposure to body fluids and tissues or excretions of infected horses. There have been no reports of any case of human-to-human transmission. The signs and symptoms of the infection include respiratory illness with flu-like symptoms. In worse cases, a person infected may develop encephalitis.
Safety, tolerability, pharmacokinetics, and immunogenicity of a human monoclonal antibody targeting the G glycoprotein of henipaviruses in healthy adults: a first-in-human, randomised, controlled, phase 1 study Playford, Elliott Geoffrey et al. The Lancet Infectious Disease, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30634-6/fulltext