Advancing RSV and hMPV research through human challenge trials
Respiratory syncytial virus (RSV) remains one of the most significant viral threats across age groups, contributing to substantial morbidity in infants, older adults, and those with underlying conditions. While recent vaccine approvals mark major progress, the development of next generation vaccines and antivirals continues to face scientific and operational challenges - particularly the unpredictability of seasonal transmission and the difficulty of generating early efficacy signals in traditional field trials.
Human challenge trials offer a complementary approach. By safely and deliberately exposing healthy adult volunteers to a well characterised virus under controlled conditions, researchers can generate rapid, precise insights into infection dynamics, immune responses, and the performance of candidate vaccines and therapeutics. hVIVO has been at the forefront of this field for decades and recently developed the world’s first RSV B human challenge model, alongside a new hMPV model.
In this Q&A, Dr Andrew Catchpole discusses the scientific rationale behind these models, how they were developed, and what they mean for the future of respiratory virus research.
RSV remains a major global health burden. What makes it such a challenging pathogen to study in traditional clinical trials?
AC: RSV is highly seasonal, unpredictable, and variable in its clinical presentation. In field trials, you are dependent on natural exposure, which means you need very large sample sizes and long study durations to capture enough cases. That makes early phase development slow and expensive. Human challenge trials overcome this by providing a controlled, predictable environment where infection, symptoms, and immune responses can be studied with precision. This is particularly valuable when you’re trying to understand mechanisms of action or make early go/no go decisions.
You’ve developed the world’s first RSV B human challenge model. Why was a B strain model needed?
Most first generation RSV vaccines were developed with only RSV A challenge virus strains to test against, specifically hVIVO’s A/Memphis strain. The Memphis strain has been the backbone of challenge studies for many years. But the field is now moving toward bivalent and trivalent vaccines that include antigens to protect against RSV A, RSV B, and often hMPV. To support that shift, we needed a robust RSV B model that mirrors what is circulating in the community today. Developing a B strain model allows us to test each component of these combination vaccines and ensure they provide broad protection.
How did you go about developing the RSV B challenge virus from initial isolate to GMP grade material?
The process begins with collecting clinical isolates - often through what we call a “friends and family” approach, where staff bring in swabs from household contacts with respiratory symptoms. Sometimes we are also able to obtain samples from patients hospitalised due to infection. We screen these samples against a broad pathogen panel and identify promising RSV B candidates. Those isolates are then tested for their ability to grow on GMP compliant cell lines, which is essential for safety and regulatory acceptance. Once a suitable isolate is identified, it undergoes minimal passage to avoid adaptation to cell culture, followed by extensive safety testing, including targeted PCR panels and next generation sequencing. The result is a well characterised, GMP manufactured challenge virus that closely reflects what is circulating in the real world.
What did the first clinical study reveal about the performance of the RSV B model?
The model produced very high infection rates - around 90% by PCR criteria - and robust symptomatic disease. Importantly, we saw strong levels of moderate to severe symptoms, which are the most relevant for translational value because they mirror the types of cases that typically present in field trials. When we compared RSV B to our established RSV A Memphis model, the B strain produced higher levels of disease across all the key endpoints. That gives us confidence that it will be highly effective for evaluating vaccines and antivirals.
How are regulators viewing data from human challenge trials, particularly for RSV?
Regulators have become increasingly receptive to challenge data when it is generated using well validated models. Several RSV vaccines received expedited designations - including Fast Track and Breakthrough designations - based in part on challenge study results. This speeds up the required regulatory package reviews later in the product development. Challenge trials can help refine dose selection, identify appropriate endpoints, and provide early efficacy signals that support progression into larger field trials. They are not a replacement for Phase III studies, but they are a powerful complement that can significantly accelerate development and can be an alternative to field based phase II studies.
What role can challenge trials play in the development of next generation vaccines and antivirals?
For vaccines, challenge studies allow you to test individual components of combination formulations — for example, the RSV A, RSV B, and hMPV elements of a trivalent vaccine. For antivirals, challenge trials offer a unique opportunity to evaluate treatment timing and dose optimisation. Traditionally, dosing is triggered by PCR positivity, but that doesn’t reflect real world behaviour. We’ve introduced patient perception triggers - essentially dosing when volunteers feel they have a cold - which better mirrors how patients seek care in the community. This makes challenge data more predictive of field performance.
You’ve also developed a new hMPV challenge model. How does this fit into the broader respiratory research landscape?
hMPV is closely related to RSV and is increasingly recognised as an important pathogen in its own right. As vaccine developers move toward combination respiratory vaccines, having validated challenge models for each component becomes essential. Our hMPV model shows strong infection rates and robust symptoms, comparable to what we see with RSV. Together, the RSV A, RSV B, and hMPV models form a comprehensive platform for evaluating next generation vaccines and therapeutics.
Looking ahead, where do you see human challenge trials making the biggest impact in respiratory virus research?
I think we’ll see challenge trials used more widely to answer early phase questions that are difficult to address in field studies - things like correlates of protection, mucosal immunity, durability, and mechanism of action. As respiratory vaccine development becomes more complex, particularly with combination products, the ability to test each component in a controlled setting will be invaluable. Challenge models won’t replace traditional trials entirely as large field trials will always be needed to fully assess safety before market authorisation, but challenge studiess will continue to play a central role in accelerating development and improving the quality of early phase decision making. We believe that a well characterised respiratory virus challenge model is an expeditious and cost effective alternative to traditional phase II studies.
As the landscape of respiratory virus research evolves, human challenge trials are emerging as a critical tool for accelerating development and improving translational confidence. The introduction of the world’s first RSV B challenge model – alongside new models for RSV A and hMPV – marks a significant step forward. By enabling precise, early phase evaluation of vaccines and antivirals, these models offer a faster, more reliable path to understanding how candidates will perform in the real world. For pathogens that continue to impose a heavy global burden, that acceleration could make a meaningful difference.
About the author
Andrew Catchpole is Chief Scientific Officer at hVIVO. He first studied as a virologist at the University of Warwick before then furthering his education with postgraduate studies for his DPhil in influenza replication at Oxford University. Since then, he has applied his scientific knowledge in a commercial setting. After working as part of a multidisciplinary R&D team developing nuclear medicine research tools at GE Healthcare, he then returned to the field of virology to work for hVIVO, an industry-leading service provider of human viral challenge studies (controlled human infection studies). Catchpole is now considered an expert in human viral challenge studies and challenge agent production having played key roles in the development of numerous challenge models at hVIVO, including influenza, RSV, HRV, SARS-CoV-2, and hMPV. He has overseen the design and conduct of numerous antiviral, immunomodulator, and vaccine product efficacy studies and now works as the CSO, leading scientific strategy for the company. A key part of his role is to provide scientific consultancy both internally and externally to hVIVO’s clients and collaborators on clinical study design, laboratory sample analysis, and data interpretation, as well as to oversee hVIVO’s challenge agent manufacturing activities.
About hVIVO
hVIVO is a full-service early phase CRO offering end-to-end drug development services from preclinical consultancy through to Phase III clinical trials, including world leading end-to-end human challenge trials services. With decades of experience in rapidly delivering data for our global client base, our team brings together strategic insight and operational expertise to deliver a variety of clinical study types across multiple locations.
To support rapid study start-up and reliable delivery, our dedicated recruitment teams in Germany and the UK provide direct access to both healthy volunteers and patient populations. This is complemented by our integrated drug development consultancy as well as our infectious disease and immunology laboratories and biobanking services.
Learn more about how hVIVO is helping to drive innovation in cardiometabolic research through deep expertise, advanced diagnostics, and end-to-end clinical support.
Visiting the RSVVW’26 Conference in Rome? Speak to the hVIVO team to learn how their RSV and HMPV challenge models are helping to shape the future of respiratory virus development.
