Clinical Pearls & Morning Reports

By Carla Rothaus

Published April 27, 2022


Do the interim findings of this trial suggest that RSVpreF vaccine has the potential to protect infants from RSV infection?

Worldwide, respiratory syncytial virus (RSV) is associated with the deaths of approximately 118,200 children annually, with approximately half the deaths occurring in infants younger than 6 months of age. Simões et al. recently reported the findings of a planned, interim analysis of a randomized, placebo-controlled, proof-of-concept, phase 2b trial that is evaluating a bivalent RSV prefusion F protein–based (RSVpreF) vaccine candidate for women in the late second or third trimester of pregnancy. Read the NEJM Original Article here.

Clinical Pearls

Q: Are there currently any therapies to prevent RSV infection?

A: Currently, no specific therapy or vaccine to treat or prevent RSV infection is available. A humanized monoclonal antibody, palivizumab, is approved to prevent serious RSV disease in infants with specific risk factors; clinical trials have shown that other monoclonal antibodies against the RSV fusion (F) protein — nirsevimab and motavizumab —have efficacy. Limitations to the use of palivizumab include the administration of multiple doses during the respiratory virus season, recommendations regarding use in only a small number of infants who are at high risk for severe RSV disease, an efficacy of approximately 45 to 55% among high-risk infants, and expense.

Q: Historically, what has hampered efforts to develop an RSV vaccine?

A: In the 1960s, immunization with a formalin-inactivated, whole-virus vaccine led to enhanced (i.e., more severe) disease after subsequent natural RSV infection in infants, and the subsequent development of vaccines has been hampered by an inability to balance side effects with immunogenicity. Vaccine-mediated enhancement of RSV disease has been observed only in persons who have not previously had RSV infection. Adults have almost universally had exposure to RSV, so the immunization of pregnant women could circumvent the risk of disease enhancement and passively protect infants before the peak incidence of RSV disease at approximately 6 weeks of age. Determination of the prefusion structure of the RSV F protein, the primary target of neutralizing antibodies, has revitalized the development of a vaccine against RSV.

Morning Report Questions

Q: Has the trial by Simões et al. raised any safety concerns to date regarding RSVpreF vaccine?

A: Eligible participants were randomly assigned in this trial, in a 1:1:1:1:1 ratio, to receive a single intramuscular injection of 120 μg or 240 μg of RSVpreF vaccine (equal parts RSV A and B antigens), formulated with or without aluminum hydroxide, or placebo. No safety concerns are reported in this interim analysis. Most systemic reactions to vaccination were mild or moderate and were similar in the RSVpreF vaccine and placebo groups. There were no appreciable between-group differences in reported unsolicited adverse events within 1 month after vaccination. Serious adverse events that occurred during the observation period were reported with similar frequency in all the groups. Overall, 170 of 403 infants (42.2%) had an adverse event in the first month of life, and the frequency of these events was similar among the trial groups. None of the adverse events in the infants were considered by the investigators to be related to maternal vaccination.

Q: Do the interim findings of this trial suggest that RSVpreF has the potential to protect infants from RSV infection?

A: The findings in this interim analysis indicate that RSVpreF vaccine elicited neutralizing titers in maternal serum obtained at deliveries that occurred, on average, approximately 7 weeks after immunization. The neutralizing titers were transferred across the placenta efficiently, and a post hoc analysis suggested that the transferred antibodies prevented medically attended RSV-associated lower respiratory tract illnesses in infants. The serologic and initial efficacy data suggest that maternal vaccination with RSVpreF vaccine during pregnancy has the potential to protect infants from RSV infection well into their first 6 months of life. This trial is ongoing in the Southern Hemisphere.

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