Researchers at The University of Queensland have achieved a breakthrough in combating two of the world's most lethal viruses, identifying the first nanobody capable of neutralizing both Nipah and Hendra viruses. The discovery offers new hope for treating these deadly henipaviruses, which currently have no approved vaccines or cures and regularly cause fatal outbreaks in humans across Asia and Australia.
Revolutionary Nanobody Technology
The nanobody, designated DS90, represents a significant advancement in antiviral therapy. Dr. Ariel Isaacs from The University of Queensland explained that "a nanobody is one-tenth the size of an antibody and being that small it can access hard-to-reach areas of a virus to block infection." This unique size advantage allows DS90 to penetrate deep viral pockets that remain inaccessible to traditional antibodies.
The research team, led by Professor Daniel Watterson and Dr. Isaacs, isolated DS90 from a series of nanobodies derived from the immune cells of an alpaca named Pedro. Camelids, including alpacas, are the only land animals that naturally produce these miniaturized antibodies, making them invaluable sources for therapeutic development.
Enhanced Viral Neutralization
Laboratory tests at UQ's School of Chemistry and Molecular Biosciences confirmed DS90's effectiveness against both target viruses. Using cryogenic electron microscopy at UQ's Centre for Microscopy & Microanalysis, researchers observed the nanobody's unique binding mechanism in unprecedented detail.
"We could see exactly how the nanobody bound to the virus reaching right into deep pockets, whereas antibodies typically just bind to exposed surfaces of viruses," Professor Watterson noted. This deeper penetration enables more effective viral neutralization by blocking the pathogens' ability to enter human cells.
Combination Therapy Prevents Viral Evolution
The research team made an additional breakthrough by combining DS90 with m102.4, a developmental antibody therapy currently used as a last-resort treatment for Hendra and Nipah infections. This combination approach yielded remarkable results in preventing viral adaptation.
"Excitingly, we demonstrated that the combination of DS90 with the m102.4 antibody – which is made at UQ – prevents Nipah virus from mutating and evolving," Dr. Isaacs reported. "This is a powerful technique to prevent new deadly variants emerging."
Clinical Significance and Disease Burden
Hendra and Nipah viruses pose significant public health threats in their respective regions. Hendra virus, first identified in Brisbane in 1994, has infected people via horses and flying foxes in eastern Australia. Meanwhile, Nipah virus outbreaks occur almost annually in Bangladesh and occasionally in other Asian countries, where the virus is carried by bats.
Both viruses cause severe respiratory and neurological disease with high fatality rates, making the development of effective treatments a critical priority. Professor Watterson emphasized that "this new information is a crucial step towards using a nanobody to combat Hendra and Nipah, which cause outbreaks in people and can often lead to fatal respiratory and neurological disease."
Manufacturing and Stability Advantages
Beyond their therapeutic potential, nanobodies offer practical advantages for drug development and deployment. Dr. Isaacs highlighted that "nanobodies are also easier to produce and more stable at higher temperatures than traditional antibodies," characteristics that could prove essential for rapid response during outbreaks in resource-limited settings.
Pandemic Preparedness Platform
The discovery emerged from a broader collaboration with Universidad Austral de Chile, where Professor Alejandro Rojas-Fernandez developed a platform capable of isolating nanobodies against viruses of concern. "Together with UQ, we aimed to construct a broad barrier against future pandemic viruses based on scalable antiviral nanobodies – this fantastic work is just the beginning," Professor Rojas-Fernandez stated.
Path to Clinical Translation
The research team is now focused on translating their laboratory findings into clinical applications. Dr. Isaacs noted that "other nanobodies have been approved for use as cancer treatments and it is now exciting to see that nanobodies can also be used to neutralise viruses."
The next phase involves developing DS90 into a therapeutic ready for clinical deployment during potential outbreaks. "The next step will be to translate our findings into a therapeutic to be clinically ready in case of an outbreak of Hendra in Australia or Nipah in Asia," Dr. Isaacs explained.
The research, conducted in collaboration with scientists at CSIRO's Australian Centre for Disease Preparedness and the University of Science and Technology of China, has been published in Nature Structural and Molecular Biology, marking a significant milestone in the fight against these deadly emerging viruses.
