It’s a confusing picture out there on what is really going on with hMPV infections globally currently. Since early January hMPV (or human metapneumovirus if we are to use its’ full name) has been in our news feed nearly daily following reports from a significant surge of infections in China. In recent days, China has reported that the rate of new hMPV infections in their county is now declining. However, the reports from China have led to a flood of articles across the news outlets, some with quite inflammatory headlines and others with a more balanced approach. Taken out of context, reports that cases have doubled within a week in the USA can sound alarming, but this is a virus known to circulate in winter and spring so such patterns are not unusual and within what we would expect for this and other seasonal respiratory viruses.
Among my fellow virologists, hMPV was of course well known as an important respiratory pathogen before it became headline news earlier this month. Despite the COVID pandemic creating many “armchair virologists”, I think it’s fair to say, that, prior to January, hMPV was not a household name. In fact, much of the general public had never heard of hMPV. Pictures of overwhelmed hospitals from virus infections naturally bring back recent memories from the onset of the COVID pandemic so this, coupled with the virus name being unfamiliar, explains the understandable concern raised.
It was great to see the highly respected and trusted WHO stepping in to clarify exactly what they understood to be the picture in China and that “surge” of hMPV infections was in fact within normal expected levels for this time of year. During Dr Harris’ statement, she was keen to point out that actually most new respiratory infections in China were still being caused by seasonal influenza and not hMPV, reminding us that flu remains the more significant burden and highest impact on struggling health systems with the levels of hospitalisations caused.
Nonetheless, hMPV is an important pathogen so I welcome the fact that this virus has been brought to the attention of the world’s media this month. Greater awareness of the viruses that continue to cause significant human disease and suffering is surely a good thing; raised awareness typically leads to greater research funding and ultimately improved medical countermeasures. Whilst hMPV is already well known within the scientific community, it is not nearly as well studied as influenza and RSV (Respiratory Syncytial Virus), either at an academic level or by industry in developing vaccines and treatments. This is perhaps not surprising given that hMPV was not discovered until 2001, so far more recently than RSV or influenza which we have known about for much longer. Furthermore, it was long considered extremely difficult to produce effective vaccines against the Pneumoviridae - the virus family for which both RSV and hMPV are members. This started to change with the discovery of the importance of the pre-fusion formation of RSV’s F protein as the appropriate vaccine target. Vaccines designed to elicit antibodies specifically targeted against the pre-fusion formation of virus’ F protein, known as the pre-F vaccines, have totally changed the paradigm and demonstrated that effective vaccines are possible.
Developing a vaccine based on any completely new construct or scientific approach always carries risks, particularly regarding the ability to achieve the desired protective effect. Human viral challenge models have long been considered an ideal way to mitigate the risk of an expensive large-scale vaccine trial failure. This is because they involve the direct inoculation of healthy study participants with the virus of interest, which, therefore, allows for direct testing of vaccine efficacy in a highly controlled setting and requires far fewer study participants than conventional trials to determine vaccine efficacy. hVIVO is very proud of its significant role in bringing the world’s first efficacious RSV vaccines to market via the use of their RSV challenge model. The model provided the first-ever demonstration of vaccine efficacy in humans for the RSV pre-F vaccines. This breakthrough led to multiple RSV pre-F vaccines being tested in the model and the successful proof-of-concept results from these challenge studies were pivotal in fast-tracking the RSV vaccines to market.
I was delighted to have observed a couple of years ago that the RSV vaccine success led some of those biotech and pharma RSV research teams to turn their attention to hMPV. Consequently, there are now a number of promising hMPV vaccines in the development pipeline. Albeit most have not yet reached the development stage of efficacy testing in humans and none have yet demonstrated efficacy to prevent or significantly reduce the hMPV disease burden.
Following this trend of RSV vaccine research teams to convert to working on hMPV, over the past year or so, hVIVO have utilised their challenge model development expertise to develop an hMPV challenge model, which culminated in a pilot challenge study late last year. As reported earlier last week, the pilot study was highly successful in demonstrating that an effective hMPV challenge model could be established with good infection rates observed and, as expected, in a safe and controlled manner. There are high hopes that the hMPV challenge model can help fast-track the development of hMPV vaccines, just as the RSV model did for RSV vaccines, to ultimately gain some control over this important global pathogen and save lives.
Thought Leadership piece by Andrew Catchpole - Chief Scientific Officer
Andrew 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). Andrew is now considered an expert in human viral challenge studies having played key roles in the development of influenza, RSV, HRV and SARS-CoV-2 challenge models at hVIVO. He has overseen the design and conduct of numerous antiviral, immunomodulator and vaccine product efficacy studies and now works as Chief Scientific Officer, leading scientific strategy for the company. A key part of his CSO role is to provide scientific consultancy both internally and externally to hVIVO’s clients and collaborators on challenge study design, laboratory sample analysis and data interpretation as well as to oversee hVIVO’s challenge agent manufacturing activities.