Respiratory Syncytial Virus (RSV) is a widespread respiratory pathogen that often causes mild, cold-like symptoms but can lead to severe illness, especially in vulnerable populations like infants and older adults, sometimes requiring hospitalization. The F protein is a primary area of scientific research, and understanding this protein has been important in developing strategies to combat RSV infections.
The F Protein: Structure and Function
The F protein, or fusion glycoprotein, is a surface protein found on the outer envelope of the RSV. It enables the virus to merge with and infect host cells. This process allows the virus to replicate.
The F protein exists in two distinct conformational states: a pre-fusion state and a post-fusion state. In its pre-fusion form, the protein is ready on the viral surface. When the virus encounters a host cell, the F protein undergoes a structural rearrangement, transitioning into the post-fusion state. This change allows the protein to insert itself into the host cell membrane, pulling the viral and cellular membranes together to facilitate fusion.
Why the F Protein is a Key Target
The F protein is a primary target for preventing RSV due to its characteristics. Its sequence is highly conserved across different RSV strains. This conservation makes it an effective target for interventions, allowing for broad protection.
The F protein’s role in viral entry makes it susceptible to neutralization by antibodies. Antibodies that specifically target the pre-fusion form of the F protein are effective at neutralizing the virus and preventing infection. These antibodies block the F protein from undergoing the conformational changes necessary for membrane fusion. The discovery and stabilization of this pre-fusion conformation have significantly advanced vaccine development efforts.
Interventions Targeting the F Protein
Knowledge of the F protein, especially its pre-fusion state, has advanced RSV prevention strategies. Researchers have focused on developing interventions that either stimulate the body to produce antibodies against the pre-fusion F protein or directly provide such antibodies.
Pre-fusion F protein-based vaccines have been developed and approved for specific populations. RSVpreF vaccines, such as Abrysvo (Pfizer) and Arexvy (GSK), are authorized for use in pregnant individuals and older adults. When administered to pregnant individuals, these vaccines induce antibodies in the mother that are transferred across the placenta, providing passive immunity to the newborn for their first several months of life. For older adults, these vaccines stimulate an antibody response, offering protection against severe RSV-associated lower respiratory tract disease.
Monoclonal antibody therapies also target the F protein to provide passive immunity. Nirsevimab (Beyfortus) is a monoclonal antibody designed to prevent RSV disease in neonates and infants. This antibody binds to the RSV pre-fusion F protein, preventing viral entry into cells. Nirsevimab has an extended serum half-life, allowing for season-long protection, typically lasting up to five months, with a single intramuscular dose. This offers immediate protection, which is especially beneficial for infants whose immune systems are still developing.