Respiratory Syncytial Virus (RSV) Vaccines for Adults Ages 60 and Older and to Protect Newborns
Health Letter, December 2023
By Michael T. Abrams, M.P.H., Ph.D.
Senior Health Researcher, Public Citizen’s Health Research Group
Severe respiratory syncytial virus infection (RSV) is an important cause of hospitalization among the very old and the very young. In 2019, industrialized countries experienced 470,000 RSV-associated hospitalizations and 33,000 in-hospital deaths among adults age 60 and older.[1] In the United States, annual estimates for childhood (<5 years of age) hospitalizations are 58,000 to 80,000 per year.[2] The Centers for Disease Control and Prevention (CDC) recognizes RSV as the leading cause of infant hospitalization.
In 2023, the Food and Drug Administration (FDA) approved two vaccines (AREXVY and ABRYSVO) to prevent RSV lower respiratory tract disease in adults ages 60 and older. Soon after those approvals, the CDC recommended that pregnant persons and older adults consult with their physicians about obtaining one of these two vaccines in anticipation of the cold and flu season.
One of the vaccines (Abrysvo by Pfizer) has also been approved for use during weeks 32 through 36 of pregnancy to protect newborns from severe RSV lower respiratory tract infection from birth through 6 months of age.
Background on RSV
RSV is an airborne virus[3] that can cause lower respiratory tract disease and symptoms including cough, runny nose, headache, fever and, in more severe cases, difficulty breathing. In most patients, the virus manifests as a cold lasting less than 5 days. The contagious period usually spans two days prior to the onset of symptoms to eight days after symptoms begin.[4]
Developing the vaccine for RSV has been challenging. Recently, there has been a breakthrough involving engineering a vaccine that utilizes pre- rather than post-fusion parts of the virus as a key ingredient. Fusion refers to the virus’s ability to attach to cells that it infects. The pre-fusion form of the surface protein is different than the post-fusion form, and that difference is important to developing a useful antigen for making a vaccine. An antigen is any substance that causes the immune system to produce antibodies against it; the antibodies help the body to fight off future attacks by organisms containing the antigen, in this case the RSV virus.
The two vaccines, Arexvy[5],[6] and Abrysvo,[7] contain pre-fusion antigens. Both vaccines are delivered by intramuscular injection and contain the same antigen; Abrysvo also contains a second antigen, making it bivalent.[8]
Efficacy and safety of the RSV vaccines
A randomized trial to test the effectiveness of Arexvy to prevent RSV-associated disease in persons age 60 years or older involved 12,467 subjects receiving the vaccine and 12,499 receiving a placebo vaccine. About 8% of of the subjects were ages 80 and older. For every 1,000 persons studied over an average of one year following immunization, it was estimated that there were 7 (0.7%) cases of RSV-associated lower respiratory tract disease in the Arexvy group compared to 40 (4%) such cases in the placebo group. Lower respiratory tract disease in this study was defined as the presence of at least two symptoms or signs (cough, sputum, shortness of breath, wheezing, increased respiratory rate).[9] The most common adverse reactions were injection site pain, fatigue, muscle aches, headache and joint stiffness.
Clinical data leading to FDA approval of Arexvy included two other trials with 2,500 subjects ages 60 and older. In one trial, Arexvy was delivered with an influenza vaccine. In the combined RSV and influenza vaccine trial, two participants developed disseminated encephalomyelitis, a rare inflammation that affects the brain and spinal cord, and one of these patients died. In the second trial, with RSV vaccine alone, one case of Guillain-Barre syndrome (a rare immune disorder that damages nerves causing muscle weakness and paralysis) was observed. These findings led the FDA to require a postmarketing study of Arexvy that further assesses the risk of such serious adverse events.
The effectiveness of Abrysvo as compared to placebo was assessed in a randomized, double-blind trial in adults ages 60 and older; 17,197 subjects received Abrysvo and 17,186 subjects received a placebo. Of the participants, 6 percent were age 80 or older. The primary endpoint was the emergence of RSV-associated lower respiratory tract disease with at least two symptoms. Based on evaluable data from just over 16,300 subjects in each group, and a median follow-up of seven months post-vaccination, Abrysvo vaccine was estimated to reduce the number of RSV-associated lower respiratory tract disease cases from 33 to 11. Unlike the large Arexvy trial, a limitation of the large Abrysvo trial is that immunocompromised individuals were excluded.
In a second randomized, double-blind trial, Abrysvo was compared to placebo in pregnant persons; 3,495 pregnant persons received Abrysvo and 3,480 pregnant persons received placebo. Six months after birth, severe lower respiratory tract disease caused by RSV occurred in 19 infants exposed in utero to Abrysvo and in 62 infants exposed to placebo. The frequency of RSV-related hospitalizations among newborns was also significantly lower in the Abrysvo group.
In individuals 60 years of age and older, the most commonly reported adverse reactions were fatigue, headache, pain at the injection site and muscle pain. In pregnant individuals, the most commonly reported adverse reactions were pain at the injection site, headache, muscle pain and nausea.
The safety of Abrysvo in pregnant persons was also assessed. From vaccination through 6 months post-partum, maternal high blood pressure and preeclampsia were more common in the Abrysvo than the placebo group. Preterm births were also more common in the Abrysvo (n=202) than the placebo (n=169) group, although only 83 and 80 infants, respectively, had an extended hospitalization for this reason. The available data were deemed “insufficient to establish or exclude a causal relationship between preterm birth and Abrysvo.” Accordingly, the FDA has required the manufacturer to conduct postmarketing studies of the potential risk of preterm birth.[10]
Studies of the co-administration of RSV vaccine with influenza or other (tetanus, diphtheria, pertussis) vaccines have thus far been inconclusive. Until more data become available, it may be best to receive RSV separately from other vaccines.[11]
What You Can Do
If you are age 60 or older or pregnant, discuss with your clinician whether you should receive an RSV vaccine. Older adults are at especially high risk of severe RSV if they have chronic illnesses including lung, heart, kidney, liver, neurologic or immune-compromising disease or diabetes, or if they reside in a nursing home.[12] During pregnancy, RSV vaccination is recommended during weeks 32 through 36, but not earlier so as to mitigate concerns about preterm birth.
Nirsevimab for prevention of RSV lower respiratory track disease in infants and children up to 24 months of age
In 2023, the FDA also approved nirsevimab (BEYFORTUS), a RSV-preventive antibody, which the CDC has recommended for some infants and young children.[13],[14] The antibody targets the pre-fusion form of a surface protein of the RSV virus. The drug is delivered via a single intramuscular injection. The approval was primarily based on data from two randomized clinical trials, one of 1,453 infants and the other of 1,490 infants. Both trials were placebo-controlled; infants born prematurely and at term were included.
Both trials found that nirsevimab protects infants and toddlers from RSV lower resipiratory tract disease for at least 150 days. Jointly, these studies found that 2% of infants receiving nirsevimab had RSV severe enough to require medical attention, compared to 7% of those receiving placebo. Across both studies, about 1% of infants had adverse reactions, which were mostly mild to moderate in severity.
The CDC recommends the neonates and infants born during or entering their first RSV season (fall through spring) receive a single dose of nirsevimab within 1 week after birth.[15] Most newborns whose mothers received the RSV vaccine during pregnancy do not need nirsevimab too.[16] Infants born outside of the RSV season and who are younger than 8 months as they enter their first RSV season should receive a single dose shortly before the season begins, but may receive a dose at any time during the season.
The CDC further recommends that older infants and toddlers (9 to 19 months) be considered for nirsevimab if they are at increased risk of severe RSV disease.
In October 2023, the CDC issued a nirsevimab shortage alert for the 2023-2024 RSV season, and recommended that the drug be prioritized for infants less than 6 months of age who were born prematurely (<29 weeks) or infants who otherwise have significant immune, heart, lung or neuromuscular conditions that place them at increased risk for lower respiratory infection.[17] Rural Native Americans up to 19 months of age also should be prioritized as they have an approximately three times higher risk of RSV hospitializaiton compared to the general U.S. infant and toddler population.[18]
References
[1] Papi A, Ison MG, Langley JM, et al. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med. 2023;388(7):595-608.
[2] U.S. Centers for Disease Control and Prevention. Respiratory syncytial virus infection (RSV). August 4, 2023. https://www.cdc.gov/rsv/high-risk/infants-young-children.html. Accessed October 30, 2023.
[3] Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: recommendations of the Advisory Committee on Immunization Practices – United States, 2023. Am J Transplant. 2023;23(10):1631-1640.
[4] Linder KA. RSV infection in older adults. JAMA. 2023;330(12):1200.
[5] GlaxoSmithKline Biologicals. Label: respiratory syncytial virus vaccine, adjunvanted (AREXVY). May 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Arexvy/pdf/AREXVY.PDF. Accessed October 30, 2023.
[6] U.S. Food and Drug Administration News Release. FDA approves first respiratory syncytial virus (RSV) vaccine. May 3, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-respiratory-syncytial-virus-rsv-vaccine. Accessed October 30, 2023.
[7] Pfizer. Label: respiratory syncytial virus vaccine (ABRYSVO). August 2023. https://www.fda.gov/media/171482/download?attachment. Accessed October 16, 2023.
[8] Two vaccines (Arexvy and Abrysvo) for prevention of RSV disease. Med Lett Drugs Ther. 2023;65(1686):155-156.
[9] Papi A, Ison MG, Langley JM, et al. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med. 2023;388(7):595-608.
[10] Harris E. Medical news in brief. FDA approves maternal RSV vaccine. JAMA. 2023;330(11):1029.
[11] Two vaccines (Arexvy and Abrysvo) for prevention of RSV disease. Med Lett Drugs Ther. 2023;65(1686):155-156.
[12] Linder KA. RSV infection in older adults. JAMA. 2023;330(12):1200.
[13] U.S. Food and Drug Administration News Release. FDA approves new drug to prevent RSV in babies and toddlers. July 17, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-prevent-rsv-babies-and-toddlers. Accessed November 9, 2023.
[14] AstraZeneca. Label: nirsevimab-alip (BEYFORTUS). July 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf. Accessed November 9, 2023. [p.1 under indication]
[15] U.S. Center for Disease Control and Prevention. Respiratory syncytial virus infection (RSV). August 4, 2023. https://www.cdc.gov/rsv/clinical/index.html#immunizations-protect-infants. Accessed November 9, 2023.
[16] Fleming-Dutra KE, Jones JM, Roper LE, et al. Use of the Pfizer respiratory syncytial virus vaccine during pregnancy for the prevention of respiratory syncytial virus-associated lower respiratory tract disease in infants: recommendations of the Advisory Committee on Immunization Practices – United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(41):1115-1122.
[17] CDC Health Alert Network. Limited Availability of Nirsevimab in the United States—Interim CDC Recommendations to Protect Infants from Respiratory Syncytial Virus (RSV) during the 2023–2024 Respiratory Virus Season. October 23, 2023.
[18] U.S. Center for Disease Control and Prevention. Respiratory syncytial virus infection. December 18, 2020. https://www.cdc.gov/rsv/research/aip.html. Accessed November 9, 2023.