Respiratory Syncytial Virus (RSV) is a common, seasonal respiratory illness that affects millions globally each year. While often causing only mild, cold-like symptoms, the virus can lead to serious lower respiratory tract infections, particularly in the most vulnerable populations. After decades of research, a new generation of preventative tools has recently become available, generating widespread public interest in how to best protect infants and older adults from severe disease.
Contextualizing RSV and the Need for Protection
RSV represents a substantial public health threat because of its high rates of severe disease in specific age groups. Each year, the virus is responsible for millions of hospitalizations worldwide, with infants under six months of age and adults over 60 years old bearing the largest burden. Infants are especially susceptible to severe outcomes like bronchiolitis and pneumonia, which often require supportive care and hospitalization.
Historically, preventative options were limited, consisting primarily of a monthly injection of palivizumab, a monoclonal antibody. This measure was reserved only for infants at the highest risk, such as those born prematurely or with significant heart or lung conditions. Palivizumab was expensive and logistically demanding, requiring five separate injections throughout the RSV season.
The Recent Breakthroughs and Approval Timeline
These products are new, representing the first approvals of their kind for general use. The shift from research to public availability occurred rapidly, with the FDA granting multiple approvals throughout 2023. These approvals marked the first time RSV vaccines were authorized for older adults and the first time a long-acting monoclonal antibody was approved for all infants.
The first approval came in May 2023 for GSK’s vaccine, Arexvy, authorized for use in individuals 60 years of age and older. Shortly after, Pfizer’s vaccine, Abrysvo, received its first approval in May 2023 for the same older adult population. Abrysvo later received a second approval in August 2023 for use in pregnant individuals to protect their newborns. Sanofi and AstraZeneca’s long-acting monoclonal antibody, Beyfortus (nirsevimab), was approved in July 2023 for infants and select toddlers.
Understanding the Different Target Groups
The new preventative measures are highly targeted, with distinct products tailored for three groups: older adults, pregnant individuals, and infants. Older adults, generally those 60 years of age and older, are eligible for active immunization using either the Arexvy or Abrysvo vaccines. Active immunization involves administering an antigen to stimulate the recipient’s own immune system to generate a lasting protective response.
The second target group is pregnant individuals, who receive the Abrysvo vaccine typically between 32 and 36 weeks of gestation. This strategy, known as maternal immunization, provides passive immunity to the infant. The mother’s immune system creates anti-RSV antibodies, which are then transferred across the placenta to the fetus, providing protection at birth.
The third group is infants under eight months old, who are eligible to receive a single dose of the monoclonal antibody, Beyfortus. This is a form of passive immunization, where pre-made antibodies are delivered directly to the infant. This single shot provides season-long protection, which is a major advantage over the monthly dosing required by the older, high-risk-only antibody, palivizumab.
Mechanism of Action: How the New Vaccines Work
The scientific advancement that made all these new products possible centers on a single viral component: the Fusion (F) glycoprotein. The RSV virus uses this protein to fuse with and enter a host cell, but the F protein changes shape dramatically during this process. Before infection, the protein exists in a highly unstable shape known as the pre-fusion conformation.
Researchers discovered that the human immune system’s most potent neutralizing antibodies primarily recognize and bind to this unstable pre-fusion shape. The breakthrough involved stabilizing the F protein in this pre-fusion state, which created a much more effective antigen than any previously used. This stabilized protein is the core component of the new active vaccines, Arexvy and Abrysvo, which train the immune system to produce targeted antibodies.
The monoclonal antibody, Beyfortus, leverages the same structural insight but works differently. Instead of prompting the body to create its own defense, Beyfortus delivers pre-made antibodies designed to bind to this same pre-fusion F protein. By directly blocking the protein, the virus is prevented from fusing with and entering the host cell, providing immediate, passive protection for the infant.