Adult and maternal RSV vaccines reveal positive findings.
Respiratory syncytial virus (RSV) is a common respiratory virus that affects children and adults.1 Transmission occurs through contact with respiratory droplets from infected people and contaminated surfaces. Individuals infected with RSV may experience mild coldlike symptoms; however, serious complications (eg, bronchiolitis and pneumonia) can occur, resulting in hospitalization.2,3 Individuals infected with RSV are typically contagious for 3 to 8 days; however, infants and immunocompromised individuals may be contagious for up to 4 weeks.1 Additionally, patients can be contagious 1 to 2 days before symptoms appear. Pharmacists should emphasize that, as with COVID-19 infection, repeated RSV infections can occur.1,4
The following pediatric groups have an increased risk of experiencing severe RSV: premature infants, young children with congenital cardiac or pulmonary diseases, and children who are immunocompromised or who have neuromuscular disorders.1 Older adults, especially those with chronic health conditions or those who are immunocompromised, also can experience serious complications from RSV.5 An estimated 60,000 to 160,000 older adults in the United States are hospitalized annually, and approximately 6000 to 10,000 of these individuals die from causes related to RSV infection. Adults who are at high risk of developing severe RSV include individuals 65 years and older, patients with chronic cardiovascular or pulmonary disease, and those who are immunocompromised.5
From 2022 to 2023, RSV was part of a “tripledemic” that included influenza infection and COVID-19.6 RSV surges across the United States occurred much earlier than usual during the 2022-2023 RSV season; it began in late fall 2022 as opposed to midwinter 2023, likely because of a combination of factors that included a decrease in COVID-19 mitigation measures (eg, masking) that reduced infections during the previous seasons.7 According to the April 2023 issue of the CDC’s Morbidity and Mortality Weekly Report, the COVID-19 pandemic disrupted the RSV season from 2020 to 2022.8 During the prepandemic seasons 2017-2020, RSV infections typically were detected in October, were highest in December, and were seen less frequently by April of the next year (Figure).8 However, during 2020-2021 RSV season, the typical pattern did not occur—cases were detected in May, the number of affected people was greatest in July, and the season was considered to be over in January of the next year. The 2021-2022 RSV season began in May and ended in July, whereas the 2022-2023 season began in June and peaked in November.8 According to the CDC, about 50 of every 100,000 individuals were hospitalized due to RSV during the 2022-2023 season.9 These unpredictable changes should be considered for upcoming RSV seasons.
Two RSV vaccines have been approved by the FDA for adults 60 years and older.10,11,12 Additionally, there is a maternal RSV vaccine in the pipeline to protect infants.13 Reviewing the results of RSV vaccine phase 3 studies will better equip pharmacists with the necessary tools to administer these vaccines and educate patients about them before the upcoming 2023-2024 RSV season begins.
Review of RSV Vaccine Phase 3 Studies
The FDA Vaccines and Related Biologics Advisory Committee voted to support approval of both the Pfizer and GSK RSV vaccines for use in adults 60 years of age and older (see Table).10,11,14-17 On May 3, 2023, GSK’s adjuvanted RSV vaccine (Arexvy) became the first RSV vaccine to receive FDA approval for use in this age group.12 And, on May 31, 2023, Pfizer's bivalent, RSV prefusion F protein-based (RSVpreF) candidate (Abrysvo) became the second vaccine to receive FDA approval for use in this age group.10 The Advisory Committee on Immunization Practices meets in June 2023 to discuss vaccine recommendations, and the new vaccines are expected to be available prior to the 2023-2024 RSV season.18
Additionally, the FDA Advisory Committee voted in support of approval for Pfizer's maternal RSVpreF vaccine candidate in May 2023; the PDUFA decision date is expected in August 2023.13 Although both GSK’s and Pfizer's RSV vaccines for use in older adults recently received approval from the FDA, phase 3 studies are still currently underway along with research on the other RSV vaccine candidates. Positive top-line data for the Pfizer and GSK vaccines have been published in the New England Journal of Medicine.15-17
Moderna's mRNA-1345 Vaccine
Moderna’s mRNA-1345 RSV vaccine uses the same technology as used for their COVID-19 mRNA vaccines— it consists of a single mRNA sequence encoding for a stabilized preF glycoprotein.19
The FDA granted Breakthrough Therapy Designation for this vaccine based on positive top-line results from the ConquerRSV phase 3 trial (NCT05127434).19 The ongoing, randomized, double-blind, placebo-controlled study is evaluating the safety and efficacy of the mRNA-1345 vaccine against RSV-associated lower respiratory tract illness (LRTI). Top-line results showed the efficacy of the vaccine to be 83.7% (95.88% CI, 66.1%-92.2%; P < .0001) against RSV-associated LRTI defined by 2 or more symptoms and 82.4% (96.36% CI, 34.8%-95.3%; P = .0078) against such illness defined by 3 or more symptoms. Most adverse events (AEs) reported were mild to moderate in nature and included injection site pain, fatigue, headache, myalgia, and arthralgia. Moderna plans to submit its BLA to the FDA during the first half of 2023.19
Pfizer's RSVpreF vaccine (Abrysvo; older adults)
The bivalent RSVpreF vaccine offers protection against RSV A and B strains. The RENOIR study (NCT05035212) is a phase 3, multicenter, randomized, placebo-controlled trial evaluating the efficacy and safety of Pfizer’s RSVpreF vaccine in adults 60 years and older.20,21 Top-line results from a preplanned interim analysis were announced August 2022.15 The 2 primary end points evaluated were vaccine efficacy against seasonal RSV-associated LRTI associated with at least 2 or 3 signs or symptoms.
The multicenter study was conducted from August 31, 2021, through July 14, 2022, across 240 sites globally. Patients were eligible to participate in the study if they were at least 60 years of age and healthy or with stable chronic medical conditions. Study participants were randomly assigned to receive either 1 intramuscular (IM) injection of the RSVpreF vaccine, 120 μg (60 μg each of RSV A and B), or placebo. At the time of the interim analysis data cutoff date on July 14, 2022, a total of 34,284 study participants received the RSVpreF vaccine (17,215 participants) or placebo (17,069 participants). The median age of the participants was 67 years.15
The study results showed the efficacy of the RSVpreF vaccine in protecting against RSV-associated LRTI with at least 2 signs or symptoms to be 66.7 (96.66% CI, 28.8%-85.8%); its efficacy against RSVassociated LRTI with at least 3 signs or symptoms was 85.7% (96.66% CI, 32.0%-98.7%).15 The most frequently reported AEs were injection-site pain, fatigue, and headache. One case of Miller Fisher syndrome—a rare nerve disorder related to Guillain-Barr. syndrome (GBS)—occurred in the group given the RSVpreF vaccine. One patient in the vaccine group also experienced GBS. Based on these results, the study investigators concluded that the RSVpreF vaccine was both safe and effective. However, a limitation of the study was that patients who were immunocompromised—a population at risk of severe infection by RSV—were excluded from the study.5,15
Pfizer's RSVpreF vaccine (maternal)
The MATISSE (NCT04424316) study is a phase 3, double-blind, randomized, placebo-controlled trial conducted in 18 countries over 4 RSV seasons. The efficacy and safety of maternal RSVpreF vaccination is being evaluated in pregnant women at 24 to 36 weeks’ gestation. Study participants were given either the RSVpreF vaccine or placebo. The 2 primary end points were medically attended, severe, RSV-associated LRTI and medically attended, RSV-associated LRTI in infants within 90, 120, 150, and 180 days after birth.16
Women participating in the clinical trial were eligible if they were healthy, were 49 years or younger, were pregnant for 24 to 36 weeks at the time of injection, were carrying 1 fetus and having an uncomplicated pregnancy, and were not known to be at risk for pregnancy complications. The median maternal age was 29 years at the time of injection. Additionally, the median gestational age was 31.3 weeks. A total of 3682 women received the RSVpreF vaccine, and 3676 were given the placebo. At the time of the analysis, 3570 infants born to mothers who received the RSVpreF vaccine, and 3558 infants born to mothers given placebo were evaluated. At the time of the interim analysis, the efficacy of the RSVpreF vaccine was 81.8% (99.5% CI, 40.6%-96.3%) against medically attended, severe, RSV-associated LRTI in infants 90 days after birth. Over 6 months, the efficacy was 69.4% (97.58% CI, 44.3%-84.1%). These results were statistically significant.16
The second primary end point of medically attended, RSV-associated LRTI revealed that the RSVpreF vaccine was 57.1% effective (99.5% CI, 14.7%-79.8%), but these results were not statistically significant.16 Since the trial was conducted during the height of the COVID-19 pandemic when more mitigation measures were in place, it could explain why the incidence of RSV infection was lower.16,22,23 The interim analysis revealed that AEs were mostly mild to moderate with no serious safety concerns detected.16 The investigators concluded that use of the RSVpreF vaccine was safe and effective against medically attended, severe, RSV-associated LRTI in infants up to 6 months of age.
GSK's Adjuvanted RSV Vaccine (Arexvy)
GSK’s adjuvanted RSV vaccine is being tested in an ongoing phase 3, international, placebo-controlled trial (NCT04886596) evaluating its efficacy and safety.17,24 Individuals 60 years and older not enrolled in any previous or current RSV vaccine trial were eligible to participate in the study.17 The participants were selected from long-term care facilities and from within the local community.24 The primary end point was vaccine efficacy against RSV-associated LRTI.17 Patients were randomly assigned to receive either 1 injection of the adjuvanted RSV vaccine or placebo.
Of 24,966 study participants in 17 countries, 12,467 individuals received 1 dose of the adjuvanted RSV vaccine, and 12,499 individuals were given the placebo. Vaccine efficacy against RSV-associated LRTI was 82.6% (96.95% CI, 57.9%-94.1%). Additionally, efficacy of the adjuvanted RSV vaccine against severe, RSV-related LRTI was 94.1% (95% CI, 62.4%-99.9%). Most AEs reported were mild to moderate in nature.17 One case of GBS was reported in the vaccine group.25 The investigators concluded that use of the adjuvanted RSV vaccine is safe and effective in preventing RSV-associated LRTI and severe disease.17
Taking a Closer Look at GBS
GBS, a rare neurologic disorder, occurs when the immune system attacks part of the peripheral nervous system. Symptoms can range from mild weakness to severe cases of paralysis. Other symptoms include sensation changes, eye muscle weakness, vision problems, severe pain, coordination problems, arrhythmias, and gastrointestinal issues. The incidence of GBS annually is approximately 1 per 100,000 individuals. In rare cases, vaccines may also cause GBS, with older adults being at increased risk. There is no cure for GBS, but treatments that may improve symptoms and shorten recovery time are available. Intravenous immunoglobulin therapy and plasma exchange are examples of GBS treatment options.26
GBS occurred in study participants from both the Pfizer (RENOIR study) and GSK phase 3 studies, and the FDA Advisory Committee recommended postmarketing studies to follow up on the risk of GBS associated with the RSV vaccines.25,27
One case of GBS and Miller Fisher syndrome occurred 7 and 8 days, respectively, after vaccination with RSVPreF.27 GBS occurred in a 66-year-old man who also experienced a myocardial infarction, which was not considered related to administration of the RSVpreF vaccine; the patient experienced bilateral lower extremity weakness, and GBS symptoms resolved in approximately 6 months. A 66-year-old woman who participated in a study developed Miller Fisher syndrome; symptoms included coordination problems, double vision, and paresthesia of the palms and soles and completely resolved after 3 months. The FDA and investigators determined that these cases were possibly related to administration of the RSVpreF vaccine.
One 78-year-old study participant developed GBS 9 days after receiving the adjuvanted RSV vaccine; symptoms included lower limb weakness, difficulty walking, and upper limb and respiratory muscle weakness.25 The FDA and investigators determined that this case likely was caused by the vaccine. The FDA announced that GSK must perform a postmarketing study of the adjuvanted RSV vaccine to evaluate the risk of GBS and acute disseminated encephalomyelitis, a rare type of inflammation affecting the brain and spinal cord that also is listed in the package insert for the adjuvanted RSV vaccine. 12,14 Pfizer’s pharmacovigilance plans for the RSVpreF vaccine may also include discussion of GBS in the package insert and increased surveillance for this complication.
RSV Prevention Tips
Pharmacists play a vital role in educating patients about RSV prevention strategies as they wait for vaccines to become available. Encourage patients to cover coughs and sneezes with a tissue or the upper shirt sleeve instead of their hands. Individuals should also wash their hands frequently with soap and water for at least 20 seconds.28 If soap and water are not readily available, hand sanitizer that contains at least 60% alcohol can be used for hand hygiene.29 Patients with coldlike symptoms are advised to avoid close contact with infants and individuals at high risk of developing severe RSV.28 Wearing a well-fitted mask, as recommended by the CDC to prevent the spread of COVID-19, may also prevent RSV transmission,as infection occurs through similar routes.1,28,30,31 Cleaning frequently touched surfaces (eg, doorknobs, mobile devices) can also prevent RSV transmission.28
There are now 2 vaccines approved to prevent RSV-associated LRTI in adults 60 years of age and older. Studies of both the adjuvanted RSV vaccine and the RSVpreF vaccine yielded positive phase 3 efficacy and safety results. However, it is important to monitor the incidence of GBS as the vaccines are administered to a larger patient population. The maternal RSVpreF vaccine demonstrated safety and efficacy in infants aged up to 6 months. Pharmacists can help to counter vaccine hesitancy by educating patients and ensuring adequate uptake of these critical immunizations.
About The Author
Jennifer Gershman, PharmD, CPh, PACS, is a pharmacist and medical writer specializing in vaccines, drug information, medication safety, and medication therapy management.
1. Respiratory syncytial virus infection (RSV): RSV transmission. CDC. Reviewed April 26, 2023. Accessed May 15, 2023. https://www.cdc.gov/rsv/about/transmission.html
2. Respiratory syncytial virus infection (RSV). CDC. Reviewed October 28, 2022. Accessed May 15, 2023. https://www.cdc.gov/rsv/index.html
3. Respiratory syncytial virus infection (RSV): symptoms and care. CDC. Reviewed October 24, 2022. Accessed May 15, 2023. https://www.cdc.gov/rsv/about/symptoms.html
4. COVID-19: what is COVID-19 reinfection? CDC. Updated March 15, 2023. Accessed May 15, 2023. https://www.cdc.gov/coronavirus/2019-ncov/your-health/reinfection.html
5. Respiratory syncytial virus infection (RSV): RSV in older adults and adults with chronic medical conditions. CDC. Reviewed October 28, 2022. Accessed May 15, 2023. https://www.cdc.gov/rsv/high-risk/older-adults.html#:~:text=Adults%20at%20highest%20risk%20for,Adults%20with%20weakened%20immune%20systems
6. Cohen J. Will viral interference hold off the tripledemic? Science. 2022;378(6622):814-815. doi:10.1126/science.adf8989
7. Updated guidance: use of palivizumab prophylaxis to prevent hospitalization from respiratory syncytial virus infection during the 2022-2023 RSV season. American Academy of Pediatrics. Updated November 17, 2022. Accessed May 15, 2023. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/interim-guidance-for-use-of-palivizumab-prophylaxis-to-prevent-hospitalization/
8. Hamid S, Winn A, Parikh R, et al. Seasonality of respiratory syncytial virus - United States, 2017-2023. MMWR Morb Mortal Wkly Rep. 2023;72(14):355-361. doi:10.15585/mmwr.mm7214a1
9. RSV-NET interactive dashboard. CDC. Reviewed October 25, 2022. Accessed May 15, 2023. https://www.cdc.gov/rsv/research/rsv-net/dashboard.html
10. FDA U.S. Food and Drug Administration. BLA Approval. May 31, 2023. Accessed June 1, 2023. https://www.fda.gov/media/168890/download
11. US FDA Advisory Committee votes to support effectiveness and safety of GSK’s respiratory syncytial virus older adult vaccine candidate. Press release. GSK. March 1, 2023. Accessed May 15, 2023. https://www.gsk.com/en-gb/media/press-releases/us-fda-advisorycommittee-votes-to-support-effectiveness-and-safety-of-gsk-s-rsvolder-adult-vaccine-candidate/
12. FDA approves first respiratory syncytial virus (RSV) vaccine. Press release. FDA. May 3, 2023. Accessed May 15, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-respiratory-syncytial-virus-rsv-vaccine
13. FDA Advisory Committee votes in support of approval for Pfizer’s vaccine candidate to help prevent RSV in infants through maternal immunization. Press release. Pfizer. May 18, 2023. Accessed May 19, 2023. https://www.pfizer.com/news/press-release/press-release-detail/fda-advisory-committee-votes-support-approval-pfizers
14. Arexvy. Prescribing information. GSK; 2023. Accessed May 15, 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Arexvy/pdf/AREXVY.PDF
15. Walsh EE, P.rez Marc G, Zareba AM, et al; RENOIR Clinical Trial Group. Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. N Engl J Med. 2023;388(16):1465-1477. doi:10.1056/NEJMoa2213836
16. Kampmann B, Madhi SA, Munjal I, et al; MATISSE Study Group. Bivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. N Engl J Med. doi:10.1056/NEJMoa2216480
17. Papi A, Ison MG, Langley JM, et al; AReSVi-006 Study Group. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med. 2023; 388(7):595-608. doi:10.1056/NEJMoa2209604
18. US FDA approves GSK’s Arexvy, the world’s first respiratory syncytial virus (RSV) vaccine for older adults. Press release. GSK. May 3, 2023. Accessed May 15, 2023. https://www.gsk.com/en-gb/media/press-releases/us-fda-approves-gsk-s-arexvy-the-world-s-first-respiratorysyncytial-virus-rsv-vaccine-for-older-adults/
19. Moderna granted FDA breakthrough therapy designation for mRNA-1345, an investigational respiratory syncytial virus (RSV) vaccine candidate. Press release. Moderna. January 30, 2023.Accessed May 15, 2023. https://investors.modernatx.com/news/news-details/2023/Moderna-Granted-FDA-Breakthrough-Therapy-Designation-for-mRNA-1345-An-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Candidate/default.aspx
20. Pfizer announces positive top-line data from phase 3 trial of older adults for its bivalent respiratory syncytial virus (RSV) vaccine candidate. Press release. Pfizer. August 25, 2022. Accessed May 15, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-data-phase-3-trial-older
21. Study to evaluate the efficacy, immunogenicity, and safety of RSVpreF in adults. (RENOIR). ClinicalTrials.gov. Updated April 19, 2023. Accessed May 15, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05035212
22. CDC museum Covid-19 timeline. CDC. Reviewed March 15, 2023. Accessed May 15, 2023. https://www.cdc.gov/museum/timeline/covid19.html
23. CDC strategy for global response to COVID-19 (2020-2023). CDC. Reviewed November 10, 2022. Accessed May 15, 2023. https://www.cdc.gov/coronavirus/2019-ncov/global-covid-19/global-response-strategy.html
24. Efficacy study of GSK’s investigational respiratory syncytial virus (RSV) vaccine in adults aged 60 years and above. ClinicalTrials.gov. Updated June 30, 2022. Accessed May 15, 2023. https://clinicaltrials.gov/ct2/show/NCT04886596
25. FDA briefing document. Respiratory syncytial virus vaccine recombinant, adjuvanted (proposed trade name: Arexvy). FDA. March 1, 2023. Accessed May 15, 2023. https://www.fda.gov/media/165622/download
26. Guillain-Barr. syndrome. National Institute of Neurological Disorders and Stroke. Reviewed March 8, 2023. Accessed May 15, 2023. https://www.ninds.nih.gov/health-information/disorders/guillain-barre-syndrome
27. FDA briefing document. Respiratory syncytial virus vaccine (proposed trade name: Abrysvo). FDA. February 28, 2023. Accessed May 15, 2023. https://www.fda.gov/media/165623/download
28. RSV prevention. CDC. Reviewed October 31, 2022. Accessed May 15, 2023. https://www.cdc.gov/rsv/about/prevention.html
29. When and how to wash your hands. CDC. Reviewed November 15, 2022. Accessed May 15, 2023. https://www.cdc.gov/handwashing/when-how-handwashing.html
30. Use and care of masks. CDC. Updated May 11, 2023. Accessed May 15, 2023. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/about-face-coverings.html
31. How COVID-19 spreads. CDC. Updated August 11, 2022. Accessed May 15, 2023. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html