Commentary: Nirsevimab protects healthy infants from RSV


Imagine a time when RSV doesn’t rage through the community each year. That time would result from decades of research that uncovered RSV’s secrets and explained the only partly successful initial vaccines and prophylactic interventions (for example, palivizumab).

Key discovery: The original RSV antigen target, RSV’s fusion (F) protein, is suboptimal despite having been associated with RSV attachment to and breaching of host cell membranes.
Some amazing work showed that having antibodies block the F-protein was like putting up a shield to protect against an arrow only after the arrow had already struck its target. Indeed, the F-protein evolves only after the attachment/breach. The preattachment/breach version (prefusion protein) sits on the virus surface and is like a loaded bow with an arrow in place. The prefusion protein changes configuration when RSV contacts host cells to uncoil and release the “arrow,” creating the entry point for RSV nucleic acids.

Nirsevimab was created to glom onto the prefusion protein and prevent it from uncoiling/releasing its “arrow,” the critical event in RSV infecting a cell. So, it is not surprising that it works better than palivizumab, which targets the fusion protein.

The prefusion protein is also the target of newer vaccine candidates, including one that showed 87% efficacy against RSV challenge in adults (think of mother getting this vaccine and endowing newborns with antiprefusion antibodies; N Engl J Med. 2022;386:2377-86).

The time when RSV is not an annual scourge is closer than ever.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

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