Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets
Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based...
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creator | Chia, Min-Yuan Hu, Alan Yung-Chih Tseng, Yu-Fen Weng, Tsai-Chuan Lai, Chia-Chun Lin, Jun-Yang Chen, Po-Ling Wang, Ya-Fang Chao, Sin-Ru Chang, Jui-Yuan Hwang, Yi-Shiuh Yeh, Chia-Tsui Yu, Cheng-Ping Chen, Yee-Chun Su, Ih-Jen Lee, Min-Shi |
description | Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300 μg aluminum hydroxide, 1.5 μg HA, and 1.5 μg HA plus 300 μg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were |
doi_str_mv | 10.1371/journal.pone.0120793 |
format | Article |
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Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300 μg aluminum hydroxide, 1.5 μg HA, and 1.5 μg HA plus 300 μg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only), 17 and 80 for the unadjuvanted (HA only) group, and 190 and 640 for the adjuvanted group (HA plus adjuvant), respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0120793</identifier><identifier>PMID: 25799397</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptation, Biological ; Aluminum ; Aluminum hydroxide ; Analysis ; Animals ; Antibodies ; Antigens, Viral - immunology ; Cell culture ; Dogs ; Female ; Ferrets ; Formulations ; Hemagglutination ; Immunization ; Immunogenicity ; Influenza ; Influenza A ; Influenza A Virus, H7N9 Subtype - immunology ; Influenza A Virus, H7N9 Subtype - ultrastructure ; Influenza vaccines ; Influenza Vaccines - immunology ; Laboratories ; Lung - immunology ; Lung - pathology ; Lung - virology ; Madin Darby Canine Kidney Cells ; Orthomyxoviridae Infections - prevention & control ; Pandemics ; Preventive medicine ; Reassortant Viruses ; Respiratory tract ; Vaccines ; Viruses</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0120793-e0120793</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Chia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Chia et al 2015 Chia et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6bac77ecbafc8b2313eae806e8fcf368e8195db710b9c50f6ce6fe983fd0585d3</citedby><cites>FETCH-LOGICAL-c692t-6bac77ecbafc8b2313eae806e8fcf368e8195db710b9c50f6ce6fe983fd0585d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370571/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370571/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25799397$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tompkins, Stephen Mark</contributor><creatorcontrib>Chia, Min-Yuan</creatorcontrib><creatorcontrib>Hu, Alan Yung-Chih</creatorcontrib><creatorcontrib>Tseng, Yu-Fen</creatorcontrib><creatorcontrib>Weng, Tsai-Chuan</creatorcontrib><creatorcontrib>Lai, Chia-Chun</creatorcontrib><creatorcontrib>Lin, Jun-Yang</creatorcontrib><creatorcontrib>Chen, Po-Ling</creatorcontrib><creatorcontrib>Wang, Ya-Fang</creatorcontrib><creatorcontrib>Chao, Sin-Ru</creatorcontrib><creatorcontrib>Chang, Jui-Yuan</creatorcontrib><creatorcontrib>Hwang, Yi-Shiuh</creatorcontrib><creatorcontrib>Yeh, Chia-Tsui</creatorcontrib><creatorcontrib>Yu, Cheng-Ping</creatorcontrib><creatorcontrib>Chen, Yee-Chun</creatorcontrib><creatorcontrib>Su, Ih-Jen</creatorcontrib><creatorcontrib>Lee, Min-Shi</creatorcontrib><title>Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300 μg aluminum hydroxide, 1.5 μg HA, and 1.5 μg HA plus 300 μg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only), 17 and 80 for the unadjuvanted (HA only) group, and 190 and 640 for the adjuvanted group (HA plus adjuvant), respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted.</description><subject>Adaptation, Biological</subject><subject>Aluminum</subject><subject>Aluminum hydroxide</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens, Viral - immunology</subject><subject>Cell culture</subject><subject>Dogs</subject><subject>Female</subject><subject>Ferrets</subject><subject>Formulations</subject><subject>Hemagglutination</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Influenza</subject><subject>Influenza A</subject><subject>Influenza A Virus, H7N9 Subtype - immunology</subject><subject>Influenza A Virus, H7N9 Subtype - ultrastructure</subject><subject>Influenza vaccines</subject><subject>Influenza Vaccines - immunology</subject><subject>Laboratories</subject><subject>Lung - immunology</subject><subject>Lung - pathology</subject><subject>Lung - virology</subject><subject>Madin Darby Canine Kidney Cells</subject><subject>Orthomyxoviridae Infections - prevention & control</subject><subject>Pandemics</subject><subject>Preventive medicine</subject><subject>Reassortant Viruses</subject><subject>Respiratory tract</subject><subject>Vaccines</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYmPwDxBEQkJw0WLHiT9ukKYyWEVhEl-3lmMft67SuNhJBfx6nDWbWrQL5Atb9nNen483y55iNMWE4Tdr34dWNdOtb2GKcIGYIPeyUyxIMaEFIvcPzifZoxjXCFWEU_owOykqJgQR7DRbXOxU06vO-Tb3Nv_0bvYx19A0EwPB7cDkrrVND-0flV-yzyLfKa1dC7lWrXFGdRATkVsIAbr4OHtgVRPhybifZd_fX3ybXU4WVx_ms_PFRFNRdBNaK80Y6FpZzeuCYAIKOKLArbaEcuBYVKZmGNVCV8hSDdSC4MQaVPHKkLPs-V532_gox0ZEiSllmGOMcCLme8J4tZbb4DYq_JZeOXl94cNSqtA53YCsLdfcKmt4WZW8prU1hpW2NMowYa1OWm_H3_p6A0ZD2wXVHIkev7RuJZd-J0vCUMWGZF6NAsH_7CF2cuPi0GTVgu-v86asKDkRCX3xD3p3dSO1VKmANCGf_tWDqDwviyKVUeIiUdM7qLQMbJxOrrEu3R8FvD4KSEwHv7ql6mOU869f_p-9-nHMvjxgV6CabhV90w-mi8dguQd18DEGsLdNxkgOpr_phhxML0fTp7BnhwO6DbpxOfkLLEb85Q</recordid><startdate>20150323</startdate><enddate>20150323</enddate><creator>Chia, Min-Yuan</creator><creator>Hu, Alan Yung-Chih</creator><creator>Tseng, Yu-Fen</creator><creator>Weng, Tsai-Chuan</creator><creator>Lai, Chia-Chun</creator><creator>Lin, Jun-Yang</creator><creator>Chen, Po-Ling</creator><creator>Wang, Ya-Fang</creator><creator>Chao, Sin-Ru</creator><creator>Chang, Jui-Yuan</creator><creator>Hwang, Yi-Shiuh</creator><creator>Yeh, Chia-Tsui</creator><creator>Yu, Cheng-Ping</creator><creator>Chen, Yee-Chun</creator><creator>Su, Ih-Jen</creator><creator>Lee, Min-Shi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150323</creationdate><title>Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets</title><author>Chia, Min-Yuan ; Hu, Alan Yung-Chih ; Tseng, Yu-Fen ; Weng, Tsai-Chuan ; Lai, Chia-Chun ; Lin, Jun-Yang ; Chen, Po-Ling ; Wang, Ya-Fang ; Chao, Sin-Ru ; Chang, Jui-Yuan ; Hwang, Yi-Shiuh ; Yeh, Chia-Tsui ; Yu, Cheng-Ping ; Chen, Yee-Chun ; Su, Ih-Jen ; Lee, Min-Shi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6bac77ecbafc8b2313eae806e8fcf368e8195db710b9c50f6ce6fe983fd0585d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adaptation, Biological</topic><topic>Aluminum</topic><topic>Aluminum hydroxide</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antigens, Viral - immunology</topic><topic>Cell culture</topic><topic>Dogs</topic><topic>Female</topic><topic>Ferrets</topic><topic>Formulations</topic><topic>Hemagglutination</topic><topic>Immunization</topic><topic>Immunogenicity</topic><topic>Influenza</topic><topic>Influenza A</topic><topic>Influenza A Virus, H7N9 Subtype - immunology</topic><topic>Influenza A Virus, H7N9 Subtype - ultrastructure</topic><topic>Influenza vaccines</topic><topic>Influenza Vaccines - immunology</topic><topic>Laboratories</topic><topic>Lung - immunology</topic><topic>Lung - pathology</topic><topic>Lung - virology</topic><topic>Madin Darby Canine Kidney Cells</topic><topic>Orthomyxoviridae Infections - prevention & control</topic><topic>Pandemics</topic><topic>Preventive medicine</topic><topic>Reassortant Viruses</topic><topic>Respiratory tract</topic><topic>Vaccines</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chia, Min-Yuan</creatorcontrib><creatorcontrib>Hu, Alan Yung-Chih</creatorcontrib><creatorcontrib>Tseng, Yu-Fen</creatorcontrib><creatorcontrib>Weng, Tsai-Chuan</creatorcontrib><creatorcontrib>Lai, Chia-Chun</creatorcontrib><creatorcontrib>Lin, Jun-Yang</creatorcontrib><creatorcontrib>Chen, Po-Ling</creatorcontrib><creatorcontrib>Wang, Ya-Fang</creatorcontrib><creatorcontrib>Chao, Sin-Ru</creatorcontrib><creatorcontrib>Chang, Jui-Yuan</creatorcontrib><creatorcontrib>Hwang, Yi-Shiuh</creatorcontrib><creatorcontrib>Yeh, Chia-Tsui</creatorcontrib><creatorcontrib>Yu, Cheng-Ping</creatorcontrib><creatorcontrib>Chen, Yee-Chun</creatorcontrib><creatorcontrib>Su, Ih-Jen</creatorcontrib><creatorcontrib>Lee, Min-Shi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chia, Min-Yuan</au><au>Hu, Alan Yung-Chih</au><au>Tseng, Yu-Fen</au><au>Weng, Tsai-Chuan</au><au>Lai, Chia-Chun</au><au>Lin, Jun-Yang</au><au>Chen, Po-Ling</au><au>Wang, Ya-Fang</au><au>Chao, Sin-Ru</au><au>Chang, Jui-Yuan</au><au>Hwang, Yi-Shiuh</au><au>Yeh, Chia-Tsui</au><au>Yu, Cheng-Ping</au><au>Chen, Yee-Chun</au><au>Su, Ih-Jen</au><au>Lee, Min-Shi</au><au>Tompkins, Stephen Mark</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-23</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0120793</spage><epage>e0120793</epage><pages>e0120793-e0120793</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300 μg aluminum hydroxide, 1.5 μg HA, and 1.5 μg HA plus 300 μg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only), 17 and 80 for the unadjuvanted (HA only) group, and 190 and 640 for the adjuvanted group (HA plus adjuvant), respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25799397</pmid><doi>10.1371/journal.pone.0120793</doi><oa>free_for_read</oa></addata></record> |
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subjects | Adaptation, Biological Aluminum Aluminum hydroxide Analysis Animals Antibodies Antigens, Viral - immunology Cell culture Dogs Female Ferrets Formulations Hemagglutination Immunization Immunogenicity Influenza Influenza A Influenza A Virus, H7N9 Subtype - immunology Influenza A Virus, H7N9 Subtype - ultrastructure Influenza vaccines Influenza Vaccines - immunology Laboratories Lung - immunology Lung - pathology Lung - virology Madin Darby Canine Kidney Cells Orthomyxoviridae Infections - prevention & control Pandemics Preventive medicine Reassortant Viruses Respiratory tract Vaccines Viruses |
title | Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets |
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