Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants

RCT (n=1453) found single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections (2.6% vs. 9.5%; p<0.001) and hospitalisations (0.8% vs. 4.1%; p<0.001) than placebo throughout RSV season in healthy preterm infants.

SPS commentary:

Nirsevimab is a recombinant human immune globulin G1 kappa monoclonal antibody, that binds the highly conserved site 0 epitope present on the prefusion conformation of the RSV fusion protein. It has has an extended half-life and is being developed to protect infants for an entire RSV season with a single intramuscular dose.


According to an editorial, palivizumab, a monoclonal antibody directed against the F protein, has been shown to reduce the risk of hospitalization for RSV among infants with recognised risk factors. However, it’s modest efficacy, requirement for monthly intramuscular administration, emergence of viral strains with mutations in F protein (escape mutants), and high cost limit its usefulness. It notes that neutralising monoclonal antibodies to G protein are being studied for both prophylaxis and treatment for RSV infections, as a highly conserved domain in the G protein plays an important role in modifying the immune response in the host. It is hypothesised that a monoclonal antibody against this proinflammatory protein may reduce disease severity. It points out that most of the ~100,000 young children in US who are hospitalised annually for RSV infection have no recognised risk factors and do not qualify for monthly prophylaxis, hence reason why prophylaxis with palivizumab has a minimal effect on overall burden of RSV infection in US and elsewhere. It suggests that a more practical approach to prophylaxis would be the administration of a long-lasting monoclonal antibody to all infants born shortly before or during the RSV season, aimed at providing several months of protection, and shifting the burden of infection to older children who are at lower risk for hospitalisation.


It discusses the findings of this study and also of another study that investigated RSV F protein nanoparticle vaccination in pregnant women, which did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. It concludes overall that the results of these two trials support the development of a monoclonal antibody with an extended half-life to deliver passive immunity, as well as provide a basis for further study of nanoparticle or alternative RSV vaccines to induce a protective and durable neutralising antibody response.


New England Journal of Medicine

Resource links:


RSV F protein nanoparticle vaccine study