Researcher Highlights
The fast-evolving landscape of respiratory virus drug development

For a kid who was fascinated by viruses – he found them “pretty cool but a bit scary” – to now be at the forefront of research that could help protect us from a range of respiratory viruses is the realisation of a long-held ambition for viral immunologist Professor Nathan Bartlett.

Nathan found lots of fascinatingly scary viruses during an early-career scholarship with the Australian Centre for Disease Preparedness in Geelong, Victoria, an experience which reinforced his interest in working in virology. From there, he took up a postdoctoral position at Oxford University where his research focused primarily on developing viral vector vaccines using the vaccinia virus, a relative of the virus that causes smallpox. During this time, he learnt a great deal about genetic engineering and cemented his interest in molecular virology and immunology of viruses and vaccines.

But he knew there was something missing. He realised he wanted to be involved with clinical-facing translational research, so took up another postdoctoral position at Imperial College London with a researcher who concentrated primarily on viral exacerbations of asthma and chronic obstructive pulmonary disease (COPD). It became clear to Nathan that the logical next step was to shift his focus to respiratory medicine where, happily, he was able to continue working with those ever-fascinating viruses, particularly the most prevalent human respiratory pathogen, rhinovirus – otherwise known as the common cold virus.

Nathan’s experiences from 13 years in the UK set him on the trajectory to where he is now. He had collaborated with University of Newcastle researchers based at HMRI whilst in the UK, and eventually joined the organisation in 2015 after relocating to Newcastle, somewhere he viewed as more “climactically consistent than Geelong and London” where he could see himself settling and raising a family. Since that time, his translational research has centred on treatments for respiratory viruses, specifically rhinovirus.

“Respiratory viruses cause the clinically most impactful transmissible diseases that challenge societies. There is a huge global burden of respiratory viral infections, with some such as influenza attracting a great deal more research than others such as rhinovirus, even though rhinovirus causes a huge burden of illness,” explains Nathan.

From rhinovirus to coronavirus: a novel control and containment treatment

In his role as head of the Viral Immunology and Respiratory Disease group with HMRI, Nathan has been working to understand the early events that influence the outcome of a respiratory infection. What is the interface between the host’s airway and the virus? How do the airway’s epithelial cells sense and then respond to a virus? How is the innate immune response triggered to control, contain and prevent the viral illness from escalating? What determines whether an infection results in a mild cold, or develops into a more serious lung disease such as an asthma attack or COVID-19? He found that a lot of those early events, mediated by innate immunity, share commonalities across all viral pathogens, which enabled him to translate research that was initially focused on rhinovirus and influenza to other viruses, including coronavirus.

Since 2015, Nathan and his industry partner, Ena Respiratory, have been developing a drug to stimulate the innate immune response in the upper respiratory tract to contain a virus, and thus reduce the risk of it spreading from the upper respiratory tract into the lungs where it can escalate to a severe illness. To date, there are no products that can achieve this outcome. The translational research output is a nasal spray, with Phase 1 clinical trials starting in mid-2021.

Nathan describes his vision for the nasal spray as a protective treatment.

“I envisage a day when a person suffering from severe asthma, for example, can walk into a pharmacy and purchase a nasal spray to protect themselves. The product we’re developing will initially be for high-risk individuals including those at high risk of exposure, chronic respiratory disease or immune suppressed. They will administer the nasal spray which will immediately prime for an immune response that facilitates control of the infection in the upper respiratory tract before it has a chance to move through the airways to their lungs.”

When our global village was rapidly engulfed by the coronavirus pandemic early in 2020, Nathan quickly applied the knowledge gained studying the treatment for other respiratory viruses to help show that innate immunity can also be leveraged to tackle coronavirus, offering a potential new treatment approach for COVID-19.

Our community-based virus protective strategies are built around vaccines, but there is a large gap in respiratory virus infection control where vaccines are not available (eg rhinovirus, RSV) or don’t work as effectively as hoped (the elderly and immune suppressed) or are not being used as required (influenza, SARS-CoV-2). This is where the nasal spray will enter the market. It’s important to note that the nasal spray is not intended to take the place of a vaccine. Rather, it will help control and contain a virus, and prevent at-risk groups such as the immunosuppressed, elderly, unvaccinated or those who have not responded well to vaccination from becoming severely ill.

“The aim of the treatment is to keep respiratory viruses from travelling from the nose and throat and entering the lungs where, as we know, it can cause severe illness and death,” Nathan explains.

The real-world application of research: a gratifying experience

After 15 years of researching respiratory viruses, Nathan is proud to say that he has played a significant role in the development of a treatment targeting the upper airways which will prevent these viruses from generating a more serious disease as soon as it causes infection. He is quick to point out that, like all research endeavours, he did not achieve this alone.

He is grateful to the Hunter Medical Research Institute and Asthma Australia who provided the seed funding needed to develop the virus infection models that enabled him to work with Ena Respiratory.

Nathan believes that COVID-19 is going to change the landscape of respiratory virus drug development moving forward. Treatments are now a major global focus, and it’s imperative that research and investment in that area continue to improve.

“I have no doubt that there will be a lot of other medications developed on the back of the urgency around COVID-19. The offshoot of that is that we will soon see better treatments for other viral diseases including RSV bronchiolitis, influenza, and asthma and COPD exacerbations. Playing a role in that has been a gratifying experience.”