Respiratory Syncytial Virus (RSV) is a common respiratory pathogen causing infections of the lungs and breathing passages. While it causes mild, cold-like symptoms for most healthy individuals, RSV poses a serious threat to specific populations, particularly infants and older adults, often leading to hospitalization. The currently approved and widely used RSV vaccines and preventative therapies are not live attenuated vaccines. They rely instead on modern, non-live technologies to protect against severe illness.
How Live Attenuated Vaccines Differ From Others
Live attenuated vaccines (LAVs) utilize a weakened, but still living, form of a virus or bacterium to stimulate an immune response. This weakened pathogen can replicate within the body, mimicking a natural infection without causing severe disease. LAVs typically elicit a strong and long-lasting immune response, often requiring only one or two doses for protection.
The use of a live pathogen presents safety considerations for individuals with compromised immune systems or very young infants. This constraint led researchers to pursue alternative technologies, such as non-live or subunit vaccines. Subunit vaccines present the immune system with only a specific protein component of the virus, rather than the whole organism. This protein, such as the RSV fusion (F) protein, trains the immune system to recognize the threat without risk of infection from the vaccine itself.
Another category of non-live prevention is passive immunity, which relies on monoclonal antibodies rather than an active vaccine. Unlike a vaccine that prompts the body to produce its own antibodies, a monoclonal antibody product delivers laboratory-made antibodies directly to the recipient. This approach provides immediate, temporary protection and is distinct from traditional vaccination, which aims to build long-term memory.
Current Approved RSV Prevention Methods
The preventative landscape for RSV utilizes two primary non-live strategies to protect different age groups. For older adults, approved products like Arexvy and Abrysvo are subunit vaccines. These immunizations target the prefusion form of the RSV F-protein, which is the shape the protein takes just before the virus fuses with a host cell membrane. Stabilizing the F-protein in this prefusion state enhances the immune response, leading to high efficacy against severe lower respiratory tract disease in adults aged 60 and older.
Abrysvo is also approved for maternal immunization, allowing the passive transfer of protective antibodies to newborns. When administered to pregnant individuals between 32 and 36 weeks of gestation, the antibodies generated by the mother’s immune system cross the placenta. This provides the infant with protection against severe RSV disease through the first six months of life.
For direct protection of infants, the primary method involves monoclonal antibodies, such as nirsevimab (Beyfortus). This preventative measure is not a vaccine but a single injection of a long-acting antibody designed to neutralize the virus. Nirsevimab binds to the F-protein on the surface of the virus, blocking it from entering the infant’s cells. This passive immunity offers protection throughout the typical five-month RSV season and is recommended for all infants under eight months of age entering their first RSV season.
Historical Context of RSV Vaccine Development
Initial attempts to develop an RSV vaccine in the 1960s used a formalin-inactivated RSV (FI-RSV) vaccine, which contained a killed form of the whole virus. When children who received this experimental vaccine were later exposed to the natural virus, many developed a severe condition known as enhanced respiratory disease (ERD).
This paradoxical outcome resulted in increased hospitalizations and two infant deaths, causing a decades-long halt in vaccine development. The FI-RSV vaccine failed to generate the correct protective immune response and instead primed the immune system for a harmful reaction upon subsequent natural infection. This historical setback demonstrated that traditional methods, such as whole-virus inactivation, were not suitable for RSV.
This historical challenge is the primary reason researchers shifted their focus toward precise, non-live technologies. The goal became to isolate the exact viral component that could safely stimulate a protective immune response without risking ERD. This led to the successful development of the F-protein-targeting subunit vaccines and the prophylactic monoclonal antibody therapies currently in use.