NIH Celebrates FDA Approval of RSV Vaccine for People 60 Years of Age and Older

NIH Research Played Major Role in Development

May 4, 2023

3D imaging of Respiratory Syncytial Virus particle

Credit: NIAID

Yesterday, the Food and Drug Administration announced the approval of the first respiratory syncytial virus (RSV) vaccine approved for use in the United States. The vaccine, Arexvy, is approved for the prevention of lower respiratory tract disease caused by RSV in individuals 60 years of age and older. The approval of Arexvy, developed by GlaxoSmithKline, marks an important step toward protecting the nation from this serious respiratory disease. Although RSV is a common virus that typically causes mild, cold-like symptoms, it can be deadly to the elderly, children younger than 5 years old, people with chronic heart or lung disease, or weakened immune systems. Each year in the United States, 60,000 to 160,000 adults 65 years and older are hospitalized and as many as 10,000 die from RSV infection, according to the Centers for Disease Control and Prevention.

The FDA-approval of the first RSV vaccine represents a significant public health achievement and results from decades of American taxpayer-funded scientific discovery and research at the National Institutes of Health. In 1957—one year after the discovery of RSV—NIH scientists determined that the virus causes bronchiolitis, an inflammation and buildup of mucus in the small airways of the lung. Several clinical trials of an experimental RSV vaccine in the mid-1960s performed poorly and resulted in a cessation of RSV vaccine development for years. However, new technologies that became available in the 1980s enabled scientists to reveal RSV’s genetic sequence. As a result, scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, began focusing their attention on the proteins found on the surface of the virus as potential vaccine targets. In 1984, NIAID scientists isolated the most important of these RSV surface proteins: fusion glycoprotein—or “F” protein—which is required by the virus to infect human cells. 

During the 1990s, NIAID scientists discovered that the F protein induced a more protective immune response against RSV infection than other surface proteins. Building on this knowledge, researchers in the 2000s identified two forms of the “F” protein: its prefusion state—-the active form prior to fusing with the human cell—and its post-fusion state, a transformed protein that is no longer capable of fusion. In 2006, NIAID’s Vaccine Research Center (VRC) launched a program to determine the atomic-level structure of the F protein to inform RSV vaccine development. Using state-of-the-art structural biology techniques, NIAID researchers were able to determine structures of both prefusion and post-fusion F protein.

In a major scientific breakthrough in 2013, NIAID scientists led by the VRC’s Barney S. Graham, M.D., Ph.D., Peter D. Kwong, Ph.D., and Jason McLellan, Ph.D., found a solution: lock the F protein in its prefusion state, exposing vulnerable surfaces that elicit potent neutralizing antibodies. Animals vaccinated with prefusion F protein shape developed a superior protective immune response against RSV compared to those vaccinated with its post-fusion form. 

This prefusion F protein shape was successfully tested in several major vaccine clinical trials funded and/or conducted by NIAID beginning in 2017. The FDA-approved Arexvy RSV vaccine, which is based upon the prefusion F protein developed by NIAID scientists, was more than 80 percent effective at preventing symptomatic RSV infection when tested in people 60 years and older. Other RSV vaccines using the prefusion form of the protein and intended for the elderly and pregnant women are also anticipated for FDA review this year.  Of note, the groundbreaking use of structure-based vaccine design and the locking of viral surface proteins in their prefusion forms not only led to an approved RSV vaccine, but also was successfully applied in 2020 in a much-more compressed timeline to develop safe and effective COVID-19 vaccines. 

Today, we celebrate the NIAID scientists and their collaborators who applied evolving technologies over many years to better understand the basic science of RSV and lay the groundwork for a vaccine to prevent severe disease. This monumental effort and the dedication of clinical trial volunteers, research staff and others working in collaboration with academic partners and the pharmaceutical industry will no doubt prevent thousands of elderly people from being hospitalized and dying from RSV infection each year. 

For more information about NIAID’s contributions to the now FDA-approved RSV vaccine.