A monoclonal antibody injection for prevention of RSV disease
Beyfortus was approved to prevent RSV lower respiratory tract disease by the FDA in July of 20231,2 in:
- Neonates and infants born during or entering their first RSV season
- Children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season
Beyfortus is a recombinant human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody (mAb) designed to prevent respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants.1
Unlike infection or vaccination, RSV antibody therapy does not stimulate the immune system. Instead, mAbs provide direct protection against disease, representing a form of passive immunization against RSV disease.2 Protection is typically at its peak in the weeks following administration of Beyfortus® but diminishes gradually over time.2
How Beyfortus® protects against RSV disease by preventing membrane fusion
Beyfortus® is a protein-directed fusion inhibitor that provides long-acting passive immunity to RSV disease by binding to a conserved epitope on the RSV prefusion F protein, interfering with cellular membrane fusion, thus preventing viral entry into cells.1
The role of glycoproteins in RSV
RSV is coated with two types of glycoproteins, the attachment glycoprotein (G protein) and the fusion glycoprotein (F protein).3 Only the F protein is essential for RSV entry into cells lining the respiratory tract.3
The RSV F protein structure exists as a type I viral fusion glycoprotein that forms a trimeric complex and mediates viral entry. 4,5
Blocking viral attachment and entry into bronchial epithelial cells
Upon infection, the RSV F protein, typically responsible for facilitating pH-independent viral membrane fusion with the host-cell plasma membrane, triggers the merging of adjacent cells when expressed on the cell surface.3
This membrane fusion process results in the formation of syncytia, large multinucleated structures that can induce epithelial lesions in the upper respiratory tract.3,6 Formation of syncytia (cell-cell fusion) is what gives RSV its characteristic name.3,6
YTE substitution prolongs the half-life of Beyfortus® RSV antibody therapy
Beyfortus® RSV antibody therapy is long-acting due to a specially designed triple amino acid substitution (YTE) in its fragment crystallizable (Fc) region, increasing its affinity to the neonatal Fc receptor.8
This YTE substitution in the Fc segment of Beyfortus® prolongs its serum half-life, and is designed to provide season-long protection that extends through 5 months after injection with a single intramuscular dose. 1,8
Specifically, the YTE modification results in a long anti-RSV antibody half-life extension from 21–28 days to 87–117 days.1
Discover more about Beyfortus®
Dosing And Administration
Demonstrated Safety and Efficacy Profile¹
Fc, fragment crystallizable; IgG1κ, immunoglobulin G1 kappa; mAb, monoclonal antibody; RSV, respiratory syncytial virus; YTE, M252Y/S254T/T256E.
Important Safety Information
References: 1. Beyfortus®(nirsevimab-alip). Prescribing Information. Sanofi. 2023 [accessed 2024 Feb 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf 2. CDC. Healthcare Providers: RSV Prevention Information [Internet]. Centers for Disease Control and Prevention. 2023 [cited 2024 Feb 19]. Available from: https://www.cdc.gov/vaccines/vpd/rsv/hcp/child.html# 3. Battles MB, Langedijk JP, Furmanova-Hollenstein P, Chaiwatpongsakorn S, Costello HM, Kwanten L, et al. Molecular mechanism of respiratory syncytial virus fusion inhibitors. Nat Chem Biol. 2016 Feb;12(2):87–93. 4. Hu M, Bogoyevitch MA, Jans DA. Impact of Respiratory Syncytial Virus Infection on Host Functions: Implications for Antiviral Strategies. Physiol Rev. 2020 Oct 1;100(4):1527–94. 5. Gilman MSA, Furmanova-Hollenstein P, Pascual G, B van ’t Wout A, Langedijk JPM, McLellan JS. Transient opening of trimeric prefusion RSV F proteins. Nat Commun. 2019 May 8;10(1):2105. 6. Fraire AE, Woda BA. Respiratory Syncytial Virus. Viruses and the Lung. :95–99 7. Ahani B, Tuffy KM, Aksyuk AA, Wilkins D, Abram ME, Dagan R, et al. Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials. Nat Commun. 8. Brady T, Cayatte C, Roe TL, Speer SD, Ji H, Machiesky L, et al. Fc-mediated functions of nirsevimab complement direct respiratory syncytial virus neutralization but are not required for optimal prophylactic protection. Front Immunol. 2023 Oct11;14:1283120. 9. Domachowske JB, Department of Pediatrics, SUNY Upstate Medical University, Syracuse, NY, USA. Nirsevimab: An extended half-life monoclonal antibody for the prevention of infant respiratoy syncytial virus infection. US Respir Pulm Dis. 2021;6(1):38.
