Skip to content

Research at St Andrews

Sialic acid-binding protein Sp2CBMTD protects mice against lethal challenge with emerging influenza A (H7N9) virus

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

E.A. Govorkova, T. Baranovich, B.M. Marathe, L. Yang, M.A. Taylor, R.G. Webster, G.L. Taylor, H. Connaris

School/Research organisations

Abstract

Compounds that target the cellular factors essential for influenza virus replication represent an innovative approach to antiviral therapy. Sp2CBMTD is a genetically engineered multivalent protein that masks sialic acid-containing cellular receptors on the respiratory epithelium, which are recognized by influenza viruses. Here, we evaluated the antiviral potential of Sp2CBMTD against lethal infection in mice with an emerging A/Anhui/1/2013 (H7N9) influenza virus and addressed the mechanistic basis of its activity in vivo. Sp2CBMTD was administered to mice intranasally as a single or repeated dose (0.1, 1, 10, or 100 μg) before (day −7, −3, and/or −1) or after (6 or 24 h) H7N9 virus inoculation. A single Sp2CBMTD dose (10 or 100 μg) protected 80% to 100% of the mice when administered 7 days before the H7N9 lethal challenge. Repeated Sp2CBMTD administration conferred the highest protection, resulting in 100% survival of the mice even at the lowest dose tested (0.1 μg). When treatment began 24 h after exposure to the H7N9 virus, a single administration of 100 μg of Sp2CBMTD protected 40% of the mice from death. The administration of Sp2CBMTD induced the pulmonary expression of proinflammatory mediators (interleukin-6 [IL-6], IL-1β, RANTES, monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein-1α [MIP-1α], and inducible protein [IP-10]) and recruited neutrophils to the respiratory tract before H7N9 virus infection, which resulted in less pronounced inflammation and rapid virus clearance from mouse lungs. Sp2CBMTD administration did not affect the virus-specific adaptive immune response, which was sufficient to protect against reinfection with a higher dose of homologous H7N9 virus or heterologous H5N1 virus. Thus, Sp2CBMTD was effective in preventing H7N9 infections in a lethal mouse model and holds promise as a prophylaxis option against zoonotic influenza viruses.

Close

Details

Original languageEnglish
Pages (from-to)1495-1504
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number3
Early online date22 Dec 2014
DOIs
Publication statusPublished - Mar 2015

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Immunomodulatory Compounds

    Taylor, G. L. & Connaris, H., 30 Jul 2015, IPC No. A61K31/74, Patent No. WO2015110831 (A1)

    Research output: Patent

  2. Prevention of influenza by targeting host receptors using engineered proteins

    Connaris, H., Govorkova, E. A., Ligertwood, Y., Dutia, B. M., Yang, L., Tauber, S., Taylor, M. A., Alias, N., Hagan, R., Nash, A. A., Webster, R. G. & Taylor, G. L., 29 Apr 2014, In : Proceedings of the National Academy of Sciences of the United States of America. 111, 17, p. 6401-6406

    Research output: Contribution to journalArticle

  3. Carbohydrate Binding Molecules

    Connaris, H. & Taylor, G. L., 3 Nov 2011, IPC No. A61P31/04, Patent No. US2011269670 (A1)

    Research output: Patent

Related by journal

  1. Model-based relationship between the molecular bacterial load assay and time-to-positivity in liquid culture

    Svensson, R. J., Sabiiti, W., Kibiki, G. S., Ntinginya, N. E., Bhatt, N., Davies, G., Gillespie, S. H. & Simonsson, U. S. H., Oct 2019, In : Antimicrobial Agents and Chemotherapy. 63, 10, 15 p., e00652-19.

    Research output: Contribution to journalArticle

  2. Moxifloxacin replacement in contemporary tuberculosis drug regimens is ineffective against persistent Mycobacterium tuberculosis: in the Cornell mouse model

    Liu, Y., Pertinez, H., Davies, G. R., Gillespie, S. H., Coates, A. R. & Hu, Y., Jul 2018, In : Antimicrobial Agents and Chemotherapy. 62, 7, 9 p., e00190-18.

    Research output: Contribution to journalArticle

  3. TonB-dependent receptor repertoire of pseudomonas aeruginosa for uptake of siderophore-drug conjugates

    Luscher, A., Moynie, L., Auguste, P. S., Bumann, D., Mazza, L., Pletzer, D., Naismith, J. H. & Köhlera, T., Jun 2018, In : Antimicrobial Agents and Chemotherapy. 62, 6, 11 p., e00097-18.

    Research output: Contribution to journalArticle

  4. Genetic determinants of the pharmacokinetic variability of rifampin in Malawian adults with pulmonary tuberculosis

    Sloan, D. J., McCallum, A. D., Schipani, A., Egan, D., Mwandumba, H. C., Ward, S. A., Waterhouse, D., Banda, G., Allain, T. J., Owen, A., Khoo, S. H. & Davies, G. R., 1 Jul 2017, In : Antimicrobial Agents and Chemotherapy. 61, 7, 9 p., e00210-17.

    Research output: Contribution to journalArticle

  5. Pharmacokinetics, tolerability, and bacteriological response of rifampin administered at 600, 900, and 1,200 milligrams daily in patients with pulmonary tuberculosis

    Aarnoutse, R. E., Kibiki, G. S., Reither, K., Semvua, H. H., Haraka, F., Mtabho, C. M., Mpagama, S. G., van den Boogaard, J., Sumari-de Boer, I. M., Magis-Escurra, C., Wattenberg, M., Logger, J. G. M., te Brake, L. H. M., Hoelscher, M., Gillespie, S. H., Colbers, A., Phillips, P. P. J., Plemper van Balen, G., Boeree, M. J. & PanACEA Consortium, 1 Nov 2017, In : Antimicrobial Agents and Chemotherapy. 61, 11, e01054-17.

    Research output: Contribution to journalArticle

ID: 172305871

Top