Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) pose significant health risks, especially among infants, the elderly, and individuals with pre-existing conditions. While recent vaccine approvals represent notable progress in combating these viruses, researchers continue to face challenges in developing next-generation vaccines and antivirals. Traditional field trials often struggle with the unpredictability of seasonal transmission and the lengthy durations required to demonstrate early efficacy.
Human challenge trials have emerged as a promising alternative. By deliberately exposing healthy adult volunteers to a controlled virus, researchers can swiftly gather data on infection dynamics, immune responses, and the effectiveness of potential vaccines and treatments. hVIVO, a leader in this field, has introduced the world’s first RSV B human challenge model, alongside a new model for hMPV.
Innovative Approaches to Vaccine Development
In a recent interview, Dr. Andrew Catchpole, Chief Scientific Officer at hVIVO, shed light on the rationale behind these developments. According to Dr. Catchpole, the variability of RSV complicates traditional field trials. “You are dependent on natural exposure, which means you need very large sample sizes and long study durations to capture enough cases,” he explained. This requirement leads to slower and more expensive early-phase developments.
Human challenge trials address these issues by creating a controlled environment where researchers can observe infection and immune responses with greater precision. This approach is particularly beneficial for understanding mechanisms of action and making informed decisions earlier in the development process.
The first generation of RSV vaccines primarily utilized the A/Memphis strain for testing. However, as the field pivots towards bivalent and trivalent vaccines that include components for RSV A, RSV B, and hMPV, the need for a robust RSV B model has become critical. “Developing a B strain model allows us to test each component of these combination vaccines and ensure they provide broad protection,” Dr. Catchpole stated.
Building the RSV B Challenge Model
The creation of the RSV B challenge model involves meticulous steps, starting with collecting clinical isolates. Using a “friends and family” approach, staff members bring in swabs from household contacts showing respiratory symptoms. Additionally, samples can sometimes be obtained from hospitalized patients. These isolates are screened for potential candidates, which undergo rigorous testing to ensure their safety and efficacy.
Once a suitable isolate is identified, it is cultivated in compliance with Good Manufacturing Practices (GMP). The model produced exceptionally high infection rates—around 90% according to PCR criteria—along with significant symptomatic disease. Notably, the symptoms observed were comparable to those seen in real-world cases, enhancing the translational value of the research.
Dr. Catchpole noted that the RSV B strain demonstrated higher levels of disease across all key endpoints compared to the established RSV A Memphis model. This finding offers confidence in the model’s effectiveness for evaluating vaccines and therapeutics.
Regulatory bodies are increasingly accepting challenge data generated from validated models. Several RSV vaccines have received expedited designations, including Fast Track and Breakthrough statuses, partly based on results from challenge studies. This expedited review process can significantly accelerate product development timelines.
Challenge trials not only refine dose selection and identify appropriate endpoints but also provide early efficacy signals that support progression into larger field trials. While these trials cannot replace Phase III studies, they serve as a powerful complement, enhancing the overall development process.
The implications extend beyond vaccines. For antiviral treatments, challenge trials provide an opportunity to evaluate timing and dosage in a way that reflects real-world scenarios. Traditional dosing is typically initiated upon PCR positivity; however, hVIVO has introduced a novel approach where dosing begins when volunteers report cold-like symptoms. This strategy aligns more closely with how patients seek care in the community, making the challenge data more predictive of field performance.
As the landscape of respiratory virus research evolves, the introduction of new challenge models for hMPV is equally significant. The hMPV model demonstrates strong infection rates and symptoms comparable to those of RSV, creating a comprehensive platform for evaluating next-generation vaccines and therapeutics.
Dr. Catchpole anticipates that challenge trials will become more prevalent in addressing early-phase questions that are difficult to tackle in traditional field studies, such as correlates of protection and mechanisms of action. As respiratory vaccine development advances, particularly with complex combination products, the ability to test each component in a controlled setting will be invaluable.
The ongoing evolution of challenge models at hVIVO represents a significant step forward in respiratory virus research. By facilitating precise evaluations of vaccines and antivirals, these models promise to accelerate the pace of development, potentially making a meaningful difference in global health outcomes.
Dr. Andrew Catchpole, a virology expert with a background from the University of Warwick and Oxford University, has played a pivotal role in developing numerous challenge models at hVIVO. As part of his comprehensive approach, he oversees scientific strategy and provides consultancy on clinical study design and data interpretation.
As the RSVVW’26 Conference approaches in Rome, attendees can engage with the hVIVO team to learn about their innovative RSV and hMPV challenge models, which are shaping the future of respiratory virus development.
