Respiratory Syncytial Virus (RSV) Vaccines for Adults Ages 60 and Older and to Protect Newborns

(A version of this article appeared in the December 2023 issue of Public Citizen’s Health Letter.)

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

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.[9] 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). 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 ages 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 a 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.
 

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.