Technically Speaking — Inching Closer to Prevention of RSV Morbidity and Mortality: ACIP Reviews the Recent Data from RSV Vaccine Trials

My husband, who is an asthmatic and “seasoned," has been coughing like crazy for about a week and feeling tight chested. He’s fully vaccinated against influenza and COVID-19, and he’s tested negative using a COVID-19 home test. So now, I am left wondering — Is he infected with respiratory syncytial virus (RSV)? And, when will we be able to prevent this awful lower respiratory tract disease in patients at both ends of the age spectrum?

In the December 2021 Technically Speaking article, “Treating and Preventing RSV,” we reviewed RSV disease, the causes for the marked change in seasonality, and some of the preventive measures (e.g., long-acting monoclonal antibodies and vaccines) that are in the pipeline. Flash forward almost a year later and RSV is hitting us like a hurricane. Indeed, based on their surveillance data, the Centers for Disease Control and Prevention (CDC) recently alerted providers to “an increase in RSV detections and RSV-associated emergency department visits and hospitalizations in multiple U.S. regions, with some regions nearing seasonal peak levels.” This drastic and unusually early spike in RSV, coupled with increasing influenza activity, is putting an overwhelming strain on pediatric hospitals across the country. The good news is that this year preventive measures are much closer to licensure.

On Oct. 20, 2022, the CDC’s Advisory Committee on Immunization Practices (ACIP) heard updates on:

• RSV vaccine development for those 60 and older
• A long-acting, single-dose monoclonal antibody product for infants

Perhaps the most exciting part of the updates were projections that these products could be submitted for licensure and recommendation during 2023. Here are some of the highlights from the meeting.

Adult RSV vaccination workgroup highlights

GSK’s adjuvanted RSV preF3 vaccine was efficacious in adults 60 years and older. Efficacy was measured for both RSV A and RSV B over an entire RSV season. For those 60 years of age and older, it was 82.6% against all RSV-lower respiratory tract disease (LRTD) and 94.1% against severe RSV-LRTD. For those 70-79 years of age, efficacy was 93.8% against all RSV-LRTD. The vaccine induced robust and persistent humoral and T cell immune responses and was well tolerated and safe. The studies also demonstrated that the vaccine can be effectively and safely co-administered with influenza vaccine.

Pfizer’s bivalent RSV preF vaccine was efficacious in adults 60 years and older. Also based on contemporary RSV A and RSV B strains, Pfizer’s phase 3 vaccine trials demonstrated 90.0% efficacy against severe disease (3 or more symptoms) and 83.4% against less severe disease (2 or more symptoms) in those 65 years of age and older. Vaccine efficacy was 66.7% against RSV A and 60.1% against RSV B when considering any acute respiratory illness, including even a single minor symptom such as nasal congestion, nasal discharge or sore throat. The reported trial was performed across 240 sites in seven countries and also demonstrated safety in adults 60 years of age and older.

The Work group members made several important points:

• During the RSV season in which these vaccines were tested, disease incidence was lower than usual. Thus, the studies were underpowered to detect some of the more severe outcomes (hospitalization, death).
• Both trials are ongoing with multiple years of follow-up planned.
• The need for revaccination, and the time interval, are yet to be determined.
• Guillain Barré syndrome (GBS) is a concern. GBS was identified in one case per about 15,000 persons who received the investigational GSK vaccine and two cases per about 26,000 persons who received the investigational Pfizer vaccine. The significance of this finding remains unclear due to a lack of known baseline rates.
• Potential barriers to uptake of a novel RSV vaccine for older adults could include “lack of patient and provider awareness of RSV as an important pathogen in older adults” (I think the popular media has solved this problem recently), vaccine fatigue, the increasing complexity of the adult immunization schedule, and hesitancy to co-administer RSV vaccine with other indicated vaccines, such as influenza and COVID-19 vaccines.

Pediatric RSV vaccination workgroup highlights

Sanofi and AstraZeneca expanded on previous presentations to ACIP by presenting new data supporting the safety and efficacy of nirsevimab against medically attended RSV LRTD and hospitalization. In the study discussed, the efficacy against hospitalization was 76.8%. Efficacy following a single dose did not wane over 150 days, suggesting the potential for protection throughout the duration of a prolonged RSV season. The safety profile was also favorable, but there was some discussion related to the feasibility of administering an intramuscular injection to all infants since such a recommendation would require a combination of office administration (for those born before the season) and in-hospital administration (for those born during the season).

This workgroup plans to present a summary of the recommendation considerations, including a cost effectiveness analysis, in February 2023. If licensed, ACIP will vote on a nirsevimab recommendation at the June 2023 meeting.

Interested in participating in an RSV vaccine trial?

Check clinicaltrials.gov to see if there is a study of RSV treatments or vaccines in which you may want to participate.

Final thoughts

Can you imagine a winter without an RSV surge? It is likely that clinicians who care for the very young and the very mature will soon have new tools at their disposal for preventing this common respiratory disease. I can’t wait and neither can my favorite patient!

Resources

• For a summary of the entire Oct. 19 – 20, 2022, ACIP meeting, please see IZ Express Issue 1,659: October 26, 2022.
• To review slides and meeting minutes, check the ACIP October 2022 meeting page.