Prevention of influenza by targeting host receptors using novel engineered proteins

Connaris, Helen and Govorkova, Elena and Ligertwood, Yvonne and Dutia, Bernadette and Yang, Lei and Tauber, Sandra and Taylor, Margaret and Alias, Nadiawati and Hagan, Robert and Nash, Anthony and Webster, Robert and Taylor, Garry (2014) Prevention of influenza by targeting host receptors using novel engineered proteins. Proceedings of the National Academy of Sciences of the United States of America, 111 (17). pp. 6401-6406. ISSN 1091-6490

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There is a need for new approaches for the control of influenza given the burden caused by annual seasonal outbreaks, emergence of viruses with pandemic potential and development of resistance to current antiviral drugs. We show that novel multivalent biologics,engineered using carbohydrate-binding modules (CBMs) specific for sialic acid, mask the cell-surface receptor recognized by the influenza virus and protect mice from a lethal challenge with 2009 pandemic H1N1 influenza virus. The most promising biologic protects mice when given as a single 1 μg intranasal dose 7 days in advance of viral challenge. There is also sufficient virus replication to establish an immune response, potentially protecting the animal from future exposure to the virus. Furthermore, the biologics appear to stimulate inflammatory mediators and this may be contributing to their protective ability. Our results suggest that this host-targeted approach could provide a front-line prophylactic that has the potential to protect against any current and future influenza virus and possibly other respiratory pathogens that also utilize sialic acid as a receptor.

Item Type: Article
Keywords: drug discovery, recombinant protein therapy
Subjects: Q Science > QR Microbiology
R Medicine > RM Therapeutics. Pharmacology
Faculty / Institute: Faculty of Bioresources & Food Industry
Depositing User: Nadiawati Alias
Date Deposited: 07 Aug 2014 02:44
Last Modified: 07 Aug 2014 02:44

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