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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Veröffentlicht in:PloS one 2015-03, Vol.10 (3), p.e0120793-e0120793
Hauptverfasser: 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
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container_end_page e0120793
container_issue 3
container_start_page e0120793
container_title PloS one
container_volume 10
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
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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 &lt;10 and &lt;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. 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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 &amp; 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 &amp; 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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 &lt;10 and &lt;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
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title Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets
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