Vaccine Update: Unpacking the Headlines: Key Takeaways from 2023-2024 RSV Season

Column Author: Yvonne M Carter, MSN, APRN II, FNP-C | Nurse Practitioner, Division of Hematology/Oncology/BMT      

Column Editor: Angela Myers, MD, MPH | Pediatric Infectious Diseases; Division Director, Infectious Diseases; Medical Director, Center for Wellbeing; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Assistant Professor of Pediatrics, University of Kansas School of Medicine

Spring 2024 has brought exciting news in the realm of RSV protection. On March 7, the Centers for Disease Control and Prevention’s (CDC’s) Morbidity and Mortality Weekly Report (MMWR) included an analysis showing that immunization with nirsevimab (Beyfortus) was 90% effective in preventing infants from being hospitalized with respiratory syncytial virus (RSV).¹ A month later on April 9, Pfizer announced positive top-line results from its phase 3 clinical trial for Abrysvo (bivalent RSVpreF vaccine) in adults 18 to 59 years of age at risk for developing severe RSV-associated lower respiratory tract disease (LRTD).² Currently, Abrysvo is approved only for adults over age 60 (along with GSK’s Arexvy), as well as pregnant people during weeks 32 through 36 of gestation for protection of newborn infants in the first 6 months of life. The shared goal for both maternal RSVpreF vaccination and infant receipt of nirsevimab is to protect babies from getting severely ill with RSV during their first RSV season, as RSV is the leading cause of hospitalization for infants in the United States.¹

Nirsevimab’s phase 3 clinical trials and prelicensure data had already demonstrated 81% effectiveness against hospitalization through six months after injection and 79% effectiveness in reducing the risk of medically attended LRTD caused by RSV. However, the recent real-world evidence of 90% effectiveness from this multisite analysis firmly upholds the CDC’s recommendations for all infants to be protected by either maternal RSV vaccination or receipt of nirsevimab in infancy.^1,3 Of the 699 hospitalized infants studied between October 2023 and February 2024, approximately 1% of those who tested positive for RSV had received nirsevimab a week or more prior to developing acute respiratory illness (ARI) symptoms. Of those with a negative RSV test, 18% had received nirsevimab. While nirsevimab receipt was more common among infants with high-risk medical conditions than in those without, there was no difference in frequency of receipt of nirsevimab by preterm status or insurance type. The median time from immunization to ARI symptom onset was 45 days. Because antibody protection wanes over time, the researchers did note that effectiveness during a full season would likely be lower than what data showed through February this year.¹ Even so, this year’s data will help to prepare for the next respiratory virus season, as nirsevimab continues to be recommended for infants under 8 months during their first RSV season in addition to high-risk toddlers 8-19 months.³

Also helpful in preparing for future RSV seasons is the news released in late February that Pfizer’s Abrysvo maintained protective efficacy through two RSV seasons against both RSV A and RSV B strains after a single dose in adults age 60 and older. Phase 3 clinical trial data in this age group showed 77.8% efficacy against RSV related LRTD (with three or more symptoms) in a second full RSV season.⁴ This evidence was shared at the same time that officials met to investigate cases of Guillain-Barre syndrome (GBS) reported in adults who had received either Pfizer’s Abrysvo or GSK’s Arexvy as vaccination against RSV.⁵ While the data thus far is based on a small number of cases, an elevated risk of GBS was observed following receipt of both RSV vaccines (n=13 in Abrysvo, n<11 in Arexvy in >2 million doses total). However, officials warn that results did not remain statistically significant for Arexvy when adjusting for the positive predictive value. While this data is preliminary, officials note that safety monitoring following RSV vaccination will continue to provide more conclusive evidence of potential risk, along with considerations to inform recommendations for the future.⁵ It is also important to note that these reports were in adults age 60 and older—an important reminder for any concerned parents of pediatric patients!

When it comes to making recommendations for our pediatric patients, it is important for providers to be able to inform patients and families while also providing any necessary education. Reports of GBS in RSV vaccine recipients over age 60 may cause concern, but this finding would not be an indication to forego immunization against RSV entirely, especially in our pediatric patients. First, it will be important moving forward to remind patients and families of the difference between vaccination and monoclonal antibodies. Pediatric providers need to be able to reassure patients that nirsevimab remains safe (and favorable) in protection against severe RSV for our youngest patients. Second, the GBS concerns have been reported in RSV vaccine recipients over age 60. Maternal vaccination with Abrysvo for protection against severe RSV in newborns continues to be recommended by the CDC.³ Presently, these are the two avenues to pursue immunization against RSV for our youngest patients. There is not yet an approved RSV vaccine for older children, but the news this month regarding positive top-line results for Abrysvo in high-risk adults age 18 to 59 moves us one step closer.

Approval of Abrysvo in younger adults at increased risk for RSV could allow for increased protection in another susceptible population and help prevent transmission to our younger, vulnerable pediatric patients. The ongoing phase 3 clinical trial for Abrysvo in this age group met its primary endpoints, demonstrating an immune response non-inferior to adults age 60 and older. Participants of this trial included adults age 18 to 59 with chronic conditions such as asthma, diabetes and chronic obstructive pulmonary disease. Thus far, the study has met its diversity recruitment goals, allowing for data that more closely reflects the diverse population here in the U.S., which is great news for generalizability. In addition, safety data thus far shows that Abrysvo was well tolerated among participants, with safety findings consistent with those from previous Abrysvo studies.²

All in all, as respiratory virus season finally begins to wane and we reflect on yet another year of hard work, we can remain hopeful that the wide world of vaccines continues to expand, allowing for increased (and improved!) protection against severe RSV for the young and old alike. As we continue to make advances in modern medicine and immunization research, it is important to continue the process of shared decision-making with each patient and family. It is by working together that we will be able to protect each other. 

References:

1. Moline HL, Tannis A, Toepfer AP, et al. Early estimate of nirsevimab effectiveness for prevention of respiratory syncytial virus-associated hospitalization among infants entering their first respiratory syncytial virus season—New Vaccine Surveillance Network, October 2023-February 2024. MMWR Morb Mortal Wkly Rep. 2024;73(9):209-214. doi:10.15585/mmwr.mm7309a4
2. Pfizer announces positive top-line results from phase 3 study of ABRYSVO in adults aged 18 to 59 at increased risk for RSV disease. News release. Pfizer; April 9, 2024. Accessed April 9, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-results-phase-3-study-1
3. Respiratory syncytial virus (RSV) immunizations. Centers for Disease Control and Prevention. Accessed April 2, 2024. https://www.cdc.gov/vaccines/vpd/rsv/index.html
4. Pfizer announces positive top-line data for full season two efficacy of ABRYSVO for RSV in older adults. News release. Pfizer; February 29, 2024. Accessed March 28, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-data-full-season-two
5. Lloyd P. Preliminary analysis of Guillain-Barre syndrome (GBS) following RSV vaccination among adults 65 years and older. Presented at the Advisory Committee on Immunization Practices meeting (ACIP); February 29, 2024. Accessed March 28, 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/06-RSV-Adults-Lloyd--508.pdf