Respiratory syncytial virus (RSV) is a highly contagious disease that affects millions of people each year around the world, resulting in an estimated 160,000 deaths. In the United States, severe RSV causes 6,000 to 10,000 deaths among people 65 years of age or older.
On May 3, the U.S. Food and Drug Administration approved Arexvy, an RSV vaccine developed by pharmaceutical company GSK plc, formerly GlaxoSmithKline plc. It is the first RSV vaccine to be approved in the United States, and according to GSK’s press release, the first for older adults to be approved anywhere in the world. This is a crucial step toward improving preventative care for this deadly disease.
“The structures we determined at the APS played an important role in the development of this vaccine. The availability of light source facilities such as the APS meant that we could try multiple variants until we hit on the right one that neutralized the virus.” — Jason McLellan, University of Texas at Austin
Although Arexvy has recently been approved, its origins date back more than a decade. GSK’s vaccine is based in part on data collected at the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory, starting in 2009. Those data were collected by Jason McLellan, now a professor at the University of Texas at Austin; Peter Kwong, chief of the structural biology section at the National Institutes of Health (NIH); and Barney Graham, who retired from NIH’s National Institute of Allergy and Infectious Diseases in 2021. (Graham is now the senior advisor for global health equity at Morehouse School of Medicine.)
McLellan was a postdoctoral researcher in Kwong’s lab at NIH from 2008 to 2013. The key to the RSV vaccine he, Kwong and Graham developed was a stronger understanding of the F protein, which sticks out from the surface of the virus and makes first contact with human cells, infecting them. The protein has two conformations: prefusion, a smaller form that first makes contact with cells, and postfusion, an extended form that the protein adopts once it has finished helping the virus into those cells.
Since infection depends on the F protein achieving its postfusion mode, McLellan, Kwong and Graham focused their efforts on stabilizing the protein in its prefusion form. This would provide a target for the immune system, helping it develop neutralizing antibodies against the virus. The researchers created more than 100 different variants of the F protein before they achieved success, and parts of that work were performed at the Southeast Regional Collaborative Access Team (SER-CAT) beamline at the APS, operated by the University of Georgia.
“The structures we determined at the APS played an important role in the development of this vaccine,” McLellan said. “The availability of light source facilities such as the APS meant that we could try multiple variants until we hit on the most stabilized antigen.”
In May 2013, McLellan, Kwong, Graham and their colleagues reported success, publishing their work in Science. In November 2013, they reported a vaccine candidate for RSV that was based on a prefusion-stabilized form of the F protein. When injected into animals, that vaccine candidate elicited exceptionally high levels of neutralizing antibodies. That paper was also published in Science, and included structural work performed at SER-CAT.
“SER-CAT is honored to have played a small but important part in building the groundwork for this momentous lifesaving vaccine,” said B.C. Wang, SER-CAT director. “This work illustrates the importance of making state-of-the-art resources such as SER-CAT available to the nation’s scientists.”
Since then, various permutations of that vaccine have undergone clinical trials. Arexvy is based in part on the vaccine candidate developed by McLellan, Kwong, Graham and their fellow researchers.
In its main clinical trial, Arexvy was administered to approximately 12,500 patients age 60 or older. The vaccine was shown to reduce the risk of developing lower respiratory tract disease (LRTD), a common RSV-related illness, by 82.6 percent, and severe LRTD by 94.1 percent.
“I’m very pleased to see our hard work pay off with an approved vaccine for RSV,” McLellan said. “Vaccine development and approval takes time, but knowing that our research will result in lives saved and severe illnesses avoided is immensely gratifying.”
Since 2013, McLellan and Graham have turned their attention to coronaviruses, applying the same technique they developed for RSV to the infamous spike protein found on coronaviruses. When the COVID-19 pandemic struck in 2020, they joined with other colleagues to apply their method to inhibit the spread of the disease. They discovered that the same principle applied to the spike protein of SARS-CoV-2, the virus that causes COVID-19, and the mutations they developed were incorporated into both Pfizer’s and Moderna’s COVID-19 vaccines.
“The COVID-19 vaccines were developed and approved quickly, but it was this structural biology work by McLellan and his colleagues on other viruses, such as RSV, over more than a decade that helped make them so effective,” said Bob Fischetti, Argonne group leader and life sciences advisor to the APS director. “It’s great to see the work come full circle and result in an approved RSV vaccine. It underlines the continuing public health benefits of basic research occurring at the APS and other light sources worldwide.”
About the Advanced Photon Source
The U. S. Department of Energy Office of Science’s Advanced Photon Source (APS) at Argonne National Laboratory is one of the world’s most productive X-ray light source facilities. The APS provides high-brightness X-ray beams to a diverse community of researchers in materials science, chemistry, condensed matter physics, the life and environmental sciences, and applied research. These X-rays are ideally suited for explorations of materials and biological structures; elemental distribution; chemical, magnetic, electronic states; and a wide range of technologically important engineering systems from batteries to fuel injector sprays, all of which are the foundations of our nation’s economic, technological, and physical well-being. Each year, more than 5,000 researchers use the APS to produce over 2,000 publications detailing impactful discoveries, and solve more vital biological protein structures than users of any other X-ray light source research facility. APS scientists and engineers innovate technology that is at the heart of advancing accelerator and light-source operations. This includes the insertion devices that produce extreme-brightness X-rays prized by researchers, lenses that focus the X-rays down to a few nanometers, instrumentation that maximizes the way the X-rays interact with samples being studied, and software that gathers and manages the massive quantity of data resulting from discovery research at the APS.
This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.
Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.
The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.