A broadly neutralizing human monoclonal antibody is effective against H7N9
Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2016
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| Online Access: | http://hdl.handle.net/1721.1/102129 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0003-0771-9889 |
| _version_ | 1826193830591856640 |
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| author | Tharakaraman, Kannan Subramanian, Vidya Viswanathan, Karthik Sloan, Susan Yen, Hui-Ling Barnard, Dale L. Leung, Y. H. Connie Szretter, Kristy J. Koch, Tyree J. Delaney, James C. Babcock, Gregory J. Sasisekharan, Ram Shriver, Zachary Wogan, Gerald N |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Tharakaraman, Kannan Subramanian, Vidya Viswanathan, Karthik Sloan, Susan Yen, Hui-Ling Barnard, Dale L. Leung, Y. H. Connie Szretter, Kristy J. Koch, Tyree J. Delaney, James C. Babcock, Gregory J. Sasisekharan, Ram Shriver, Zachary Wogan, Gerald N |
| author_sort | Tharakaraman, Kannan |
| collection | MIT |
| description | Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (−24 h) or double-dose (−12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (−12 h) combined with oseltamivir at 50 mg/kg (−12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains. |
| first_indexed | 2024-09-23T09:46:04Z |
| format | Article |
| id | mit-1721.1/102129 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:46:04Z |
| publishDate | 2016 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1021292022-09-26T13:35:50Z A broadly neutralizing human monoclonal antibody is effective against H7N9 Tharakaraman, Kannan Subramanian, Vidya Viswanathan, Karthik Sloan, Susan Yen, Hui-Ling Barnard, Dale L. Leung, Y. H. Connie Szretter, Kristy J. Koch, Tyree J. Delaney, James C. Babcock, Gregory J. Sasisekharan, Ram Shriver, Zachary Wogan, Gerald N Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. School of Engineering Koch Institute for Integrative Cancer Research at MIT Tharakaraman, Kannan Subramanian, Vidya Wogan, Gerald N. Sasisekharan, Ram Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (−24 h) or double-dose (−12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (−12 h) combined with oseltamivir at 50 mg/kg (−12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains. National Institutes of Health (U.S.) (Merit Award R37 GM057073-13) Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology) 2016-04-04T17:15:51Z 2016-04-04T17:15:51Z 2015-09 2014-11 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/102129 Tharakaraman, Kannan, Vidya Subramanian, Karthik Viswanathan, Susan Sloan, Hui-Ling Yen, Dale L. Barnard, Y. H. Connie Leung, et al. “A Broadly Neutralizing Human Monoclonal Antibody Is Effective Against H7N9.” Proc Natl Acad Sci USA 112, no. 35 (August 17, 2015): 10890–10895. https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0003-0771-9889 en_US http://dx.doi.org/10.1073/pnas.1502374112 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Tharakaraman, Kannan Subramanian, Vidya Viswanathan, Karthik Sloan, Susan Yen, Hui-Ling Barnard, Dale L. Leung, Y. H. Connie Szretter, Kristy J. Koch, Tyree J. Delaney, James C. Babcock, Gregory J. Sasisekharan, Ram Shriver, Zachary Wogan, Gerald N A broadly neutralizing human monoclonal antibody is effective against H7N9 |
| title | A broadly neutralizing human monoclonal antibody is effective against H7N9 |
| title_full | A broadly neutralizing human monoclonal antibody is effective against H7N9 |
| title_fullStr | A broadly neutralizing human monoclonal antibody is effective against H7N9 |
| title_full_unstemmed | A broadly neutralizing human monoclonal antibody is effective against H7N9 |
| title_short | A broadly neutralizing human monoclonal antibody is effective against H7N9 |
| title_sort | broadly neutralizing human monoclonal antibody is effective against h7n9 |
| url | http://hdl.handle.net/1721.1/102129 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0003-0771-9889 |
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