Clinician Article

Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults.

  • Papi A
  • Ison MG
  • Langley JM
  • Lee DG
  • Leroux-Roels I
  • Martinon-Torres F, et al.
N Engl J Med. 2023 Feb 16;388(7):595-608. doi: 10.1056/NEJMoa2209604. (Original)
PMID: 36791160
Read abstract
  • Geriatrics
    Relevance - 7/7
    Newsworthiness - 7/7
  • Public Health
    Relevance - 7/7
    Newsworthiness - 6/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 7/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 6/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 6/7
  • Infectious Disease
    Relevance - 6/7
    Newsworthiness - 6/7
  • Respirology/Pulmonology
    Relevance - 6/7
    Newsworthiness - 6/7


BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection.

METHODS: In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01E-adjuvanted RSV prefusion F protein-based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20%. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated.

RESULTS: A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR-confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups.

CONCLUSIONS: A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting conditions. (Funded by GlaxoSmithKline Biologicals; AReSVi-006 ClinicalTrials.gov number, NCT04886596.).

Clinical Comments

Family Medicine (FM)/General Practice (GP)

That is good to know. When the vaccine is ready, I will definitely recommend my patients get it.

General Internal Medicine-Primary Care(US)

This is new and important information. RSV is well known as a threat to young children, however, it results in the death of far more older adults than children. If the vaccine is approved, it should be administered as a standard of care for persons 60+ who do not have a contraindication.


As a practising geriatrician, I frequently face the issue of RSV infections. I am not surprised with the result of this article because I have witnessed the success of other vaccines in preventing or reducing the impact of infections. This is welcome news for the elderly.

Infectious Disease

Important trial showing effectiveness of vaccine to prevent RSV disease in older adults, which is an increasing problem.

Infectious Disease

Exciting phase 3 trial of an RSV vaccine that is safe, immunogenic, and effective in preventing disease. Although often disregarded in adults, we saw the importance of RSV this past winter with the "tridemic" of influenza, COVID, and RSV. The main limitation of this study is the lack included transplant or immunosuppressed patients. These are the patients I'd be most interested in vaccinating against RSV, but who may not be able to mount a vaccine response. I appreciate that the study looked at vaccine efficacy specifically in frail and pre-frail patients, but I found their definition of frailty, based only on gait speed, to be limited.

Internal Medicine

RSV is an important cause of URI/LRI in children and probably in adults. The vaccine against RSV with an efficacy of 84% and 80% with minimum adverse events as shown in this trial is very relevant for clinical practice. Useful information.

Internal Medicine

We have good news. A well developed RCT demonstrates for the first time the efficacy and safety of a vaccine to prevent Respiratory Syncytial Virus infection in aged persons with chronic and frailty conditions, at least for one RSV session.


A large study demonstrating the efficacy of an RSV vaccine in participants => 60-years-old with no significant safety issues. May become another standard vaccine for eligible patients.


The prevalence and severity of RSV-induced respiratory disease in adults is highly underappreciated by clinicians. An effective vaccine is a highly desirable preventive intervention. This study reveals a potentially game-changing vaccine approach.

Register for free access to all Professional content

Want the latest in aging research? Sign up for our email alerts.

Support for the Portal is largely provided by the Labarge Optimal Aging Initiative. AGE-WELL is a contributing partner. Help us to continue to provide direct and easy access to evidence-based information on health and social conditions to help you stay healthy, active and engaged as you grow older. Donate Today.

© 2012 - 2020 McMaster University | 1280 Main Street West | Hamilton, Ontario L8S4L8 | +1 905-525-9140 | Terms Of Use