Keren Landman, Jason McLellan, and Barney Graham discuss the challenges of developing a vaccine for RSV, the impact of RSV on vulnerable populations, and the historical failures of RSV vaccines. They also explain the importance of the F protein, the process of developing a structure-based vaccine for RSV, and the successful testing of the vaccine in mice.
RSV infection can be severe, especially in babies and the elderly, causing clogged airways and difficulty in breathing.
Structure-based vaccine design, by stabilizing the pre-fusion shape of the F protein, has led to the development of effective RSV vaccines.
Deep dives
The Impact of RSV Infection
RSV infection can be severe, particularly in babies and older adults with weakened immune systems. It infects cells in the respiratory tract, leading to clogged airways and difficulty in breathing. RSV season can overwhelm hospitals, resulting in many hospitalizations and deaths each year. The development of an effective RSV vaccine has been a long-standing challenge.
The Historical Challenges of RSV Vaccine Development
Scientists started developing an RSV vaccine in the 1960s but faced a major setback when the vaccine actually made children sicker instead of protecting them. The failure was attributed to the vaccine's incorrect protein preparation, which resulted in ineffective antibody responses. One key protein, the F protein, plays a crucial role in RSV infection and vaccine development. Researchers struggled to study the protein in its original pre-fusion state, which is necessary for effective vaccine design.
Structure-Based Vaccine Design for RSV
Researcher Jason McClellan applied structure-based vaccine design, previously used for HIV, to RSV. By isolating and stabilizing the pre-fusion shape of the F protein, scientists were able to mimic the exact protein structure found on the surface of the RSV virus. Tests showed that this approach elicited the strongest neutralizing antibody response ever seen in RSV research. The success of this strategy has paved the way for the development of RSV vaccines that are now being administered to millions of people.
What is ‘structure-based’ vaccine design? Before scientists used these techniques to design vaccines against Covid, they were testing them in the lab to combat RSV. Keren Landman joins the show to talk about how this respiratory virus endangers the lives of babies and the elderly. Then, we hear about an early RSV vaccine trial that cast a shadow over modern research, and how scientists, including our guests Jason McLellan and Barney Graham, later figured out how to create and stabilize a viral antigen’s spike protein to fight RSV.