Nirsevimab

Nirsevimab is a recombinant human immunoglobulin G1 kappa (IgG1ĸ) long-acting monoclonal antibody that binds to the prefusion conformation of the respiratory syncytial virus (RSV) F protein. RSV is coated with two types of glycoproteins, the attachment glycoprotein (G protein) and the fusion glycoprotein (F protein). Of these two, only the F protein is essential for the entry of the virus into cells lining the respiratory tract, making it a desirable drug target. The RSV F protein is initially in a metastable prefusion conformation and undergoes conformational changes after being triggered by an unknown event. These conformational changes lead to a postfusion conformation, where both viral and host-cell membranes are together.

Nirsevimab binds to a highly conserved epitope of the RSV prefusion F protein, inhibiting the membrane fusion step in the viral entry process. This allows nirsevimab to neutralize various RSV A and B strains and block cell-to-cell fusion. Nirsevimab has also been modified with a triple amino acid substitution (M257Y/S259T/T261E [YTE]) in the Fc region to extend serum half-life from the typical 21–28 days to approximately 69 days.