Nirsevimab is a long-acting monoclonal antibody directed against the F protein of the respiratory syncytial virus (RSV). It contains mutations in its Fc region that allow for an extended half-life, providing protection for more than three months with a single dose.

Unlike Palivizumab, which was only indicated for high-risk infants, Nirsevimab was designed to protect all newborns during their first RSV season. Available clinical trials show effectiveness in reducing hospitalizations due to RSV infection. However, in some cases, worsening of symptoms has been reported, associated with antibody-mediated phenomena such as ADE (antibody-dependent enhancement).

Studies conducted in the United States, France, Spain, and Luxembourg demonstrate high coverage and a decrease in hospitalizations for bronchiolitis, a disease that can cause severe complications in infants if not treated promptly. The possible immunological explanation lies in its high affinity for the FcRn receptor, which modifies how lung cells process IgG bound to the virus. This may facilitate viral entry into macrophages and alter the immune response, especially when antibody concentrations are low during the first days after administration.

Key Points:

• Nirsevimab reduces RSV hospitalizations, but its true benefit may be smaller due to biases, patient exclusions, and methodological limitations.
• It has not been shown to significantly reduce hospitalizations from all causes.
• The risk of ADE has not been completely ruled out, particularly in the initial days following administration.
• The cost–benefit of universal immunization must be evaluated carefully due to its high price and the still-incomplete evidence.
• The authors recommend increased surveillance, stronger studies, and a more rigorous safety assessment.