A version of this article originally appeared on Contemporary Pediatrics.
Respiratory syncytial virus (RSV), which was first discovered in 1956, has posed a longstanding challenge for vaccine development, particularly in children. Healthcare providers have largely relied on symptomatic management and basic preventative measures such as handwashing, limiting contact with sick individuals during the newborn period, and promoting breastfeeding.
Takeaways
- Respiratory Syncytial Virus (RSV) has been a long-standing challenge for vaccine development, and healthcare providers have primarily relied on symptomatic management and preventive measures such as handwashing and breastfeeding.
- RSV continues to cause significant morbidity and mortality, particularly in children, with thousands of cases and hospitalizations each year, including 100 to 300 child deaths.
- The COVID-19 pandemic disrupted the typical seasonal pattern of RSV, leading to atypical surges in infections in 2022. It is expected to return to its usual seasonal pattern in the fall of 2023.
- Clinical manifestations of RSV range from mild respiratory symptoms to severe conditions like bronchiolitis and pneumonia, and early infection in infants can lead to reactive airway disease.
- In 2023, new preventive measures have been introduced, including a monoclonal antibody (nirsevimab-alip) for children and a vaccine (Abrysvo) for pregnant women. Efforts for RSV vaccine development are ongoing, with a focus on live-attenuated, mRNA, and vector-based vaccines.
Although the drug palivizumab (Synagis) has been available for high-risk infants, RSV continues to claim the lives of thousands of individuals each year in the United States, including 100 to 300 children. The virus remains a leading cause of respiratory-related hospitalizations, with an estimated 58,000 to 80,000 admissions annually, and virtually all children contract RSV at least once by the age of 2 years.
Before the COVID-19 pandemic, RSV typically followed a predictable seasonal pattern, starting in mid-fall and lasting through winter and early spring in temperate climates. However, during the pandemic, because of various public health measures like physical distancing and mask use, the typical RSV season did not materialize in 2020 or 2021.
Instead, there were atypical surges in RSV infections in spring and fall of 2022. The expectation is that RSV will return to its typical seasonal pattern in the fall of 2023.
Clinical manifestations of RSV include a range of respiratory symptoms, from rhinorrhea and congestion to more severe conditions like bronchiolitis and pneumonia. Complications such as secondary bacterial infections can also occur.
Babies infected with RSV early in life may be at risk of developing reactive airway disease later. Managing these symptoms often requires hospitalization and supportive care.
Efforts to develop an effective RSV vaccine have faced several challenges. Natural immunity to RSV is neither complete nor long-lasting, necessitating the development of a vaccine that can induce a stronger and more durable immune response.
Early vaccine attempts had safety concerns, and the varying demographics that stand to benefit from vaccination complicate the development process. The goal is to reduce the severity and mortality of RSV infections, but there are multiple clinical endpoints to consider.
Until 2023, only 2 pharmaceutical preventive measures were available: RSV-IGIV and palivizumab. However, these options had limitations, leading researchers to continue their efforts in developing new preventive measures. Several candidate vaccines have been evaluated in recent years.
In 2023, nirsevimab-alip (Beyfortus), a monoclonal antibody, was approved for use in children, providing passive immunization and demonstrating a significant reduction in the risk of medically attended lower respiratory tract infections in infants.
This approach simplifies immunization for infants and offers protection during the crucial RSV season. Implementation challenges include monitoring for escape variants, adjusting to changing disease epidemiology, and ensuring widespread access to this medication.
Additionally, a new RSV vaccine for pregnant women, Abrysvo, was approved in 2023 to prevent RSV-related lower respiratory tract disease in infants. However, this vaccine has some safety concerns related to preterm births and is awaiting further guidance.
Looking ahead, the pipeline for RSV vaccine development includes live-attenuated vaccines for children, mRNA vaccines, and vector-based vaccines. Researchers are also working to address delivery mechanisms for low- and middle-income countries.
While 2023 marks the introduction of new tools to combat RSV, it's clear that a combination of strategies will be necessary to reduce RSV-related morbidity in the years to come.
This article was written with the help of ChatGPT.
References:
1. Karron, RA. Respiratory syncytial vaccines and monoclonal antibodies. In: Orenstein WA, Offit PA, Edward KM, Plotkin SA, eds. Plotkin’s Vaccines. 8th ed. Elsevier; 2024:998-1004.
2. Shi T, Balsells E, Wastnedge E, et al. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: systematic review and meta-analysis. J Glob Health. 2015;5(2):020416. doi:10.7189/jogh.05.020416
3. Mineva GM, Purtill H, Dunne CP, Philip RK. Impact of breastfeeding on the incidence and severity of respiratory syncytial virus (RSV)-associated acute lower respiratory infections in infants: a systematic review highlighting the global relevance of primary prevention. BMJ Glob Health. 2023;8(2):e009693. doi:10.1136/bmjgh-2022-009693
4. Committee on Infectious Diseases and Bronchiolitis Guidelines Committee, Brady MT, Byington CL, et al. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-420. doi:10.1542/peds.2014-1665
5. Respiratory syncytial virus (RSV) surveillance. Accessed August 29, 2023. https://www.cdc.gov/surveillance/nrevss/rsv/index.html
6. 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
7. Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360(6):588-598. doi:10.1056/NEJMoa0804877
8. Borchers AT, Chang C, Gershwin ME, Gershwin LJ. Respiratory syncytial virus—a comprehensive review. Clin Rev Allergy Immunol. 2013;45(3):331-379. doi:10.1007/s12016-013-8368-9
9. Mejias A, Rodríguez-Fernández R, Oliva S, Peeples ME, Ramilo O. The journey to a respiratory syncytial virus vaccine. Ann Allergy Asthma Immunol. 2020;125(1):36-46. doi:10.1016/j.anai.2020.03.017
10. McLellan JS, Yang Y, Graham BS, Kwong PD. Structure of respiratory syncytial virus fusion glycoprotein in the postfusion conformation reveals preservation of neutralizing epitopes. J Virol. 2011;85(15):7788-7796. doi:10.1128/JVI.00555-11
11. Graham BS. Vaccine development for respiratory syncytial virus. Curr Opin Virol. 2017;23:107-112. doi:10.1016/j.coviro.2017.03.012
12. Rocca A, Biagi C, Scarpini S, et al. Passive immunoprophylaxis against respiratory syncytial virus in children: where are we now? Int J Mol Sci. 2021;22(7):3703. doi:10.3390/ijms22073703
13. ACIP and AAP recommendations for the use of the monoclonal antibody nirsevimab for the prevention of RSV disease. In: Red Book Online, 2023. Accessed August 29, 2023. https://publications.aap.org/redbook/resources/25379/
14. Hammitt LL, Dagan R, Yuan Y, et al; MELODY Study Group. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med. 2022;386(9):837-846. doi:10.1056/NEJMoa2110275
15. Esposito S, Abu Raya B, Baraldi E, et al. RSV prevention in all infants: which is the most preferable strategy? Front Immunol. 2022;13:880368. doi:10.3389/fimmu.2022.880368
16. Diethelm-Varela B, Soto JA, Riedel CA, Bueno SM, Kalergis AM. New developments and challenges in antibody-based therapies for the respiratory syncytial virus. Infect Drug Resist. 2023;16:2061-2074. doi:10.2147/IDR.S379660
17. FDA approves first vaccine for pregnant individuals to prevent RSV in infants. News release. FDA. Updated August 22, 2023. Accessed August 28, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-vaccine-pregnant-individuals-prevent-rsv-infants#:~
18. McAleese S. A look at what is in the pipeline for RSV vaccines for children. Contemporary Pediatrics. May 5, 2023. Accessed August 29, 2023. https://www.contemporarypediatrics.com/view/a-look-at-what-is-in-the-pipeline-for-rsv-vaccines-for-children
