Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published February 15, 2023


In the trial by Papi et al., how effective was one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease?

There is currently no licensed vaccine against respiratory syncytial virus (RSV) infection. Papi et al. recently reported the initial findings of an ongoing, phase 3, placebo-controlled trial that is assessing the efficacy of a single dose of an RSV prefusion F protein candidate vaccine against RSV-related lower respiratory tract disease in adults 60 years of age or older. Read the NEJM Original Article here.

Clinical Pearls

Q: Is RSV infection only life-threatening among the very young?

A: Most children are infected with RSV by 2 years of age, but reinfection may recur throughout life, typically with mild or no symptoms. In older adults or those with coexisting conditions, RSV infection can cause lower respiratory tract disease, which may lead to exacerbation of underlying diseases, hospitalization, and death. In 2019, RSV infection accounted for an estimated 5.2 million cases of acute respiratory infection, 470,000 hospitalizations, and 33,000 in-hospital deaths among adults 60 years of age or older in industrialized countries.

Q: What is considered an advantage of the vaccine being tested in this trial?

A: Most RSV vaccine candidates being tested in clinical trials target the RSV F glycoprotein, which mediates viral fusion and host-cell entry, elicits neutralizing antibodies, and is highly conserved across the two RSV subtypes (A and B). A candidate RSV vaccine for older adults (RSVPreF3 OA) contains F protein stabilized in its prefusion conformation, which exposes epitopes targeted by neutralizing antibodies. Immunization of mice and macaques with stabilized prefusion forms of the F protein elicited significantly higher neutralizing activity than postfusion forms.

Morning Report Questions 

Q: In the trial by Papi et al., how effective was one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease?

A: The authors are conducting this trial in 17 countries in Africa, Asia, Australia, Europe, and North America. Participants are followed for three consecutive RSV seasons in the Northern Hemisphere and for at least two consecutive seasons in the Southern Hemisphere. The current report presents results for the first RSV season in the Northern Hemisphere. In total, 47 participants (7 of 12,466 in the vaccine group and 40 of 12,494 in the placebo group) in the modified exposed population (all the participants who had received vaccine or placebo and did not report an RSV-related acute respiratory infection before day 15 after injection) reported an episode of RSV-related lower respiratory tract disease during a median follow-up of 6.7 months (maximum follow-up, 10.1 months). The vaccine efficacy was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1). Vaccine efficacy was similar against the RSV A and B subtypes and was consistently high among participants 60 to 69 years of age and those 70 to 79 years of age, among prefrail older adults, and among those with coexisting conditions.

Q: What were the safety results in this study of the RSVPreF3 OA vaccine?

A: The RSVPreF3 OA vaccine was more reactogenic than placebo, but most reactions were mild or moderate and transient. No imbalances were observed between the vaccine group and the placebo group in the overall incidences of serious adverse events, injection-related serious adverse events, fatal serious adverse events, potential immune-mediated diseases, or injection-related potential immune-mediated diseases, although careful monitoring is warranted as larger numbers of persons are vaccinated.

Browse more Clinical Pearls & Morning Reports »

NEJM Knowledge+