As the global health community continues to grapple with the pervasive challenge of influenza and its ever-evolving strains, a new study published in “Antiviral Research” sheds light on a promising avenue in antiviral therapy: single-domain antibodies (sdAbs). The article, titled “Promises and Challenges of Single-Domain Antibodies to Control Influenza” (DOI: 10.1016/j.antiviral.2024.105807), authored by Arne Matthys and Xavier Saelens from the VIB Center for Medical Biotechnology and Ghent University in Belgium, discusses the potential for sdAbs to revolutionize the way we prevent and treat influenza virus infections.
The Quadrivalent Vaccine and Antiviral Medications
Influenza, a contagious respiratory illness caused by influenza viruses, leads to significant morbidity and mortality worldwide. In response, the World Health Organization recommends the use of a quadrivalent vaccine for prophylaxis against the illness, aiming to prevent severe disease and to accommodate the antigenic diversity of circulating influenza strains. Despite the existence of these vaccines and an array of small molecule antivirals designed to treat influenza, the persistent emergence of drug-resistant viruses presents a formidable challenge to public health.
Enter Single-Domain Antibodies
Antibody-based antivirals offer an alternative to small molecules and conventional monoclonal antibodies. Among them, sdAbs—also known as nanobodies—are gaining attention. These are antibodies consisting of a single monomeric variable antibody domain, which can bind selectively to a specific part of an antigen. They are characterized by their high specificity, stability, and ease of production. The surface of the influenza A and B virions is decorated with hemagglutinin molecules, which sdAbs can target due to their role as receptor-binding and membrane fusion proteins.
Targeting Hemagglutinin and Beyond
The study by Matthys and Saelens specifies that sdAbs that bind to influenza A and B hemagglutinin have already been described in scientific literature, showcasing their ability to neutralize the virus. Moreover, sdAbs against the neuraminidase of influenza A virus have been reported. Neuraminidase is an enzyme that facilitates the release of progeny viruses from the host cell, and is another key target of antivirals. However, there are no reports of sdAbs targeting the neuraminidase of influenza B virus.
Another target is the matrix protein 2 (or its ectodomain) of influenza A, which has also been successfully bound by sdAbs, while the same cannot be said for the matrix protein 2 of influenza B. The matrix protein 2 forms a proton-selective ion channel that is essential for viral replication, making it a valuable target for antiviral strategies.
Challenges and the Road Ahead
Despite the optimism surrounding sdAbs, challenges remain in their development and deployment. For one, there’s the issue of influenza’s rapid mutation, which can potentially reduce the efficacy of sdAbs as the viruses evolve. Furthermore, large-scale production and regulatory approval are non-trivial hurdles that must be surmounted for sdAbs to become a mainstream option in influenza control.
Patent Landscape and Competing Interests
The authors of the study also declared competing interests in the realm of sdAbs, particularly in the patent applications that describe single-domain antibodies directed against H5N1 influenza virus HA and NA. Xavier Saelens is named as an inventor on these patents (WO2009/147248, WO2010/081856, and WO2014/090865), indicating a significant financial interest that could drive further research and development in this field.
Conclusion
The study offers a comprehensive overview of the current state and potential of sdAbs in the fight against influenza. By outlining the advantages, describing specific targets, and acknowledging the challenges ahead, Matthys and Saelens provide critical insights into an emerging field that holds promise for enhancing our antiviral arsenal.
Keywords
1. Single-domain antibodies Influenza
2. Influenza antiviral resistance
3. Nanobody influenza treatment
4. Hemagglutinin neuraminidase inhibitors
5. Influenza vaccine antiviral therapy
References
1. Matthys, A. & Saelens, X. (2024). Promises and challenges of single-domain antibodies to control influenza. Antiviral Research, 105807. https://doi.org/10.1016/j.antiviral.2024.105807
2. World Health Organization. (n.d.). Influenza (Seasonal). Retrieved from https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)
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