This study presents a review of new antibody-based therapies for respiratory syncytial virus and a revised list of the most promising candidates based on the results of the latest clinical trials.
The human respiratory syncytial virus (hRSV) causes seasonal outbreaks and can result in severe outcomes for high-risk populations such as preterm children and older adults. These populations have an increased risk of lower respiratory tract disease and severe pneumonia with hRSV infection.
A study published in the journal Infection and Drug Resistance reviewed the available antibodies against hRSV and the novel antibodies under development.
Antibodies Against hRSV in Clinical Use
To date, only two drugs have been approved for clinical use against hRSV: (1) polyclonal antibodies, referred to as RSV intravenous immune globulin G (RSV-IVIG) and (2) the humanized monoclonal anti-F antibody palivizumab. Both are prophylactic agents.
Significant limitations were associated with RSV-IVIG, such as the need for many convalescent blood donors to procure it and high batch-to-batch variability. Thus, it was discontinued after the approval of palivizumab, which showed greater consistency. However, the high cost of palivizumab, moderate efficacy, a requirement for frequent administration, and use limited to prophylaxis highlight the need for developing a superior therapeutic agent.
Novel Antibody-Based Therapies
- Clinical Considerations
New agents should have a high affinity for their target to avoid off-target effects at therapeutic doses. They should have a long half-life and efficient distribution to target tissues. Humanized or fully human antibodies are preferred due to their low risk of evoking anti-immunoglobulin antibodies. Another consideration is the immunoglobulin class: while IgM and IgG elicit complement-dependent cytotoxicity, IgA is better for local administration. Neutralizing immunoglobulins targeting viral surface proteins, such as F-hRSV or G-hRSV, would be suitable for prophylaxis and early therapy.
Nirsevimab is an anti-F-hRSV neutralizing human IgG antibody. It has an extended half-life compared to palivizumab. Clinical trials have shown a 70% decrease in lower respiratory tract infections associated with hospitalizations. Consequently, it should decrease the need for immunizations, saving costs and improving patient compliance. Nirsevimab attained its first two approvals in the European Union and the United Kingdom in 2022.
Motavizumab is an anti-F-hRSV humanized neutralizing monoclonal antibody currently under investigation. It has increased potency over palivizumab; however, clinical trials have shown a lack of clear superiority of motavizumab vs. palivizumab and a high incidence of adverse effects.
- Other Neutralizing Antibodies
Suptavumab is an anti-F-hRSV antibody that was discontinued after failing phase III clinical trials. Other neutralizing antibodies in preclinical or early clinical phases are the anti-F IgA HNK20, the anti-F-hRSV antibody ALX-0171, and the anti-G-hRSV antibodies 131-2-G, 2B11, and 3D3.
- Anti-N-hRSV Antibodies
Anti-N-hRSV antibodies are under preclinical investigation. These agents are directed against a surface protein expressed by infected cells. The proposed role of these antibodies includes diagnosis by detecting N-hRSV in infected samples, and prevention and treatment of hRSV infection.
Diethelm-Varela, B., Soto, J. A., Riedel, C. A., Bueno, S. M., & Kalergis, A. M. (2023). New Developments and Challenges in Antibody-Based Therapies for the Respiratory Syncytial Virus. Infection and Drug Resistance, Volume 16, 2061–2074. https://doi.org/10.2147/idr.s379660