Structure-based Protein Design Advances Vaccine Development for Human Metapneumovirus

When the U.S. Centers for Disease Control and Prevention began investigating several cases of severe respiratory illnesses around the state of North Dakota in 2016, they uncovered the presence of a serious and potentially life-threatening virus known as human metapneumovirus (hMPV). Within four hospitals across the state, 44 cases of hMPV were uncovered impacting both children (17) and adults (27). And although many healthy populations are not severely impacted by hMPV, five of the patients from this outbreak―including two children, succumbed to the illness. hMPV like COVID-19, which would surface only three short years later, and other transient viruses suffer from the same problem: a lack of information. The cases in North Dakota show that hMPV can have serious health implications for some patient populations, but the lack of understanding about this virus, and countless others, means that there are no vaccines or therapeutics available to help protect at-risk groups. Fortunately, this issue is starting to change. In a recent study published in Nature Communications, a team of researchers carrying out experiments at the U.S. Department of Energy’s Advanced Photon Source (APS) have isolated and characterized highly stable hMPV fusion (f) proteins that are critical for viral entry. The insights reported not only provide the structure-function relationship of these fusion proteins, but also highlight the potential for these proteins to advance the development of hMPV vaccines and therapeutics.

COVID-19, which has resulted in the death of more than 6.6 million people around the world, has brought dialogue about vaccines and immunity back to the forefront of public conversation. And although devastating viral infections like polio, hepatitis A&B, Haemophilus influenzae type B, measles, and mumps have essentially been erased from the U.S. vernacular due to successful vaccination programs, few people are aware that many debilitating and long-standing viral pathogens, like chikungunya virus, Dengue virus, eastern equine encephalitis virus, cytomegalovirus, respiratory syncytial virus and a number of other viruses still lack the basic research to develop adequate vaccines and therapeutics.

Similarly, the devastating hMPV virus that struck North Dakota in 2016 lacked the basic research information for vaccine development and remains without a vaccine in 2022.

Read more on the APS website

Image: Fig. 1. Crystal structure of perfusion-stabilized hMPV F (DS-CavES2) made with ChimeraX with substitutions shown as spheres, determined at SBC-XSD.