Amino Acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge
Avian influenza A H7N7/NL/219/03 virus creates a serious pandemic threat to human health because it can transmit directly from domestic poultry to humans and from human to human. Our previous vaccine study reported that mice when immunized intranasally (i.n) with live Bac-HA were protected from leth...
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| description | Avian influenza A H7N7/NL/219/03 virus creates a serious pandemic threat to human health because it can transmit directly from domestic poultry to humans and from human to human. Our previous vaccine study reported that mice when immunized intranasally (i.n) with live Bac-HA were protected from lethal H7N7/NL/219/03 challenge, whereas incomplete protection was obtained when administered subcutaneously (s.c) due to the fact that H7N7 is a poor inducer of neutralizing antibodies. Interestingly, our recent vaccine studies reported that mice when vaccinated subcutaneously with Bac-HA (H7N9) was protected against both H7N9 (A/Sh2/2013) and H7N7 virus challenge. HA1 region of both H7N7 and H7N9 viruses are differ at 15 amino acid positions. Among those, we selected three amino acid positions (T143, T198 and I211) in HA1 region of H7N7. These amino acids are located within or near the receptor binding site. Following the selection, we substituted the amino acid at these three positions with amino acids found on H7N9HA wild-type. In this study, we evaluate the impact of amino acid substitutions in the H7N7 HA-protein on the immunogenicity. We generated six mutant constructs from wild-type influenza H7N7HA cDNA by site directed mutagenesis, and individually expressed mutant HA protein on the surface of baculovirus (Bac-HAm) and compared their protective efficacy of the vaccines with Bac-H7N7HA wild-type (Bac-HA) by lethal H7N7 viral challenge in a mouse model. We found that mice immunized subcutaneously with Bac-HAm constructs T143A or T198A-I211V or I211V-T143A serum showed significantly higher hemagglutination inhibition and neutralization titer against H7N7 and H7N9 viruses when compared to Bac-HA vaccinated mice groups. We also observed low level of lung viral titer, negligible weight loss and complete protection against lethal H7N7 viral challenge. Our results indicated that amino acid substitution at position 143 or 211 improve immunogenicity of H7N7HA vaccine against H7N7/NL/219/03 virus. |
| doi_str_mv | 10.1371/journal.pone.0128940 |
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Our previous vaccine study reported that mice when immunized intranasally (i.n) with live Bac-HA were protected from lethal H7N7/NL/219/03 challenge, whereas incomplete protection was obtained when administered subcutaneously (s.c) due to the fact that H7N7 is a poor inducer of neutralizing antibodies. Interestingly, our recent vaccine studies reported that mice when vaccinated subcutaneously with Bac-HA (H7N9) was protected against both H7N9 (A/Sh2/2013) and H7N7 virus challenge. HA1 region of both H7N7 and H7N9 viruses are differ at 15 amino acid positions. Among those, we selected three amino acid positions (T143, T198 and I211) in HA1 region of H7N7. These amino acids are located within or near the receptor binding site. Following the selection, we substituted the amino acid at these three positions with amino acids found on H7N9HA wild-type. In this study, we evaluate the impact of amino acid substitutions in the H7N7 HA-protein on the immunogenicity. We generated six mutant constructs from wild-type influenza H7N7HA cDNA by site directed mutagenesis, and individually expressed mutant HA protein on the surface of baculovirus (Bac-HAm) and compared their protective efficacy of the vaccines with Bac-H7N7HA wild-type (Bac-HA) by lethal H7N7 viral challenge in a mouse model. We found that mice immunized subcutaneously with Bac-HAm constructs T143A or T198A-I211V or I211V-T143A serum showed significantly higher hemagglutination inhibition and neutralization titer against H7N7 and H7N9 viruses when compared to Bac-HA vaccinated mice groups. We also observed low level of lung viral titer, negligible weight loss and complete protection against lethal H7N7 viral challenge. Our results indicated that amino acid substitution at position 143 or 211 improve immunogenicity of H7N7HA vaccine against H7N7/NL/219/03 virus.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0128940</identifier><identifier>PMID: 26030920</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino acid substitution ; Amino Acid Substitution - immunology ; Amino acids ; Animals ; Antibodies ; Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Antibody Formation - immunology ; Avian flu ; Avian influenza ; Baculovirus ; Binding sites ; Biotechnology ; Cell Line ; Cytotoxicity ; Female ; HA protein ; Health aspects ; Health risks ; Hemagglutination inhibition ; Immunization ; Immunization - methods ; Immunogenicity ; Influenza ; Influenza A ; Influenza A Virus, H7N7 Subtype - immunology ; Influenza A Virus, H7N9 Subtype - immunology ; Influenza Vaccines - immunology ; Low level ; Lungs ; Medical laboratories ; Mice ; Mice, Inbred BALB C ; Mutagenesis ; Neutralization ; Occupational accidents ; Orthomyxoviridae Infections - immunology ; Pandemics ; Peptides ; Proteins ; Sf9 Cells ; Site-directed mutagenesis ; Spodoptera ; Vaccination ; Vaccination - methods ; Vaccines ; Viruses</subject><ispartof>PloS one, 2015-06, Vol.10 (6), p.e0128940</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 kumar 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 kumar et al 2015 kumar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e767616a90fcace9be1eece8b39dc8ed834d905189bbc8cd10ae5cec4750569b3</citedby><cites>FETCH-LOGICAL-c692t-e767616a90fcace9be1eece8b39dc8ed834d905189bbc8cd10ae5cec4750569b3</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/PMC4452345/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452345/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26030920$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ye, Zhiping</contributor><creatorcontrib>Kumar, Subaschandrabose Rajesh</creatorcontrib><creatorcontrib>Prabakaran, Mookkan</creatorcontrib><creatorcontrib>Ashok Raj, Kattur Venkatachalam</creatorcontrib><creatorcontrib>He, Fang</creatorcontrib><creatorcontrib>Kwang, Jimmy</creatorcontrib><title>Amino Acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Avian influenza A H7N7/NL/219/03 virus creates a serious pandemic threat to human health because it can transmit directly from domestic poultry to humans and from human to human. 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Our results indicated that amino acid substitution at position 143 or 211 improve immunogenicity of H7N7HA vaccine against H7N7/NL/219/03 virus.</description><subject>Amino acid substitution</subject><subject>Amino Acid Substitution - immunology</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>Antibody Formation - immunology</subject><subject>Avian flu</subject><subject>Avian influenza</subject><subject>Baculovirus</subject><subject>Binding sites</subject><subject>Biotechnology</subject><subject>Cell Line</subject><subject>Cytotoxicity</subject><subject>Female</subject><subject>HA protein</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Hemagglutination inhibition</subject><subject>Immunization</subject><subject>Immunization - methods</subject><subject>Immunogenicity</subject><subject>Influenza</subject><subject>Influenza A</subject><subject>Influenza A Virus, H7N7 Subtype - immunology</subject><subject>Influenza A Virus, H7N9 Subtype - immunology</subject><subject>Influenza Vaccines - immunology</subject><subject>Low level</subject><subject>Lungs</subject><subject>Medical laboratories</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mutagenesis</subject><subject>Neutralization</subject><subject>Occupational accidents</subject><subject>Orthomyxoviridae Infections - immunology</subject><subject>Pandemics</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Sf9 Cells</subject><subject>Site-directed mutagenesis</subject><subject>Spodoptera</subject><subject>Vaccination</subject><subject>Vaccination - methods</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>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNklGL1DAQx4so3nn6DUQDguDDrknTpM3LwbKou7B64um9hjSddrO0ydqkh-enN3fbO7agIHnIZPKbfybDP0leEjwnNCfvd27orWrne2dhjklaiAw_Sk6JoOmMp5g-PopPkmfe7zBmtOD8aXKSckyxSPFp8nvRGevQQpsKXQ6lDyYMwTjr0brb9-4aUNhCjLvBugas0SbcIFejVf4lXy3Q194FMBYpWx1iHdBnowGpRhnrA9pA2Kr2DkdXpo_hMp5bsA08T57UqvXwYtzPkh8fP3xfrmabi0_r5WIz01ykYQY5zznhSuBaKw2iBAKgoSipqHQBVUGzSmBGClGWutAVwQqYBp3lDDMuSnqWvD7o7lvn5Tg2LwkvMiEYxVkk1geicmon973pVH8jnTLyLuH6Rqo-GN2CTFXKGBMqx5hkVHCFCQWREqpqXjGRR63z8bWh7KDSYEP89UR0emPNVjbuWmYZS2nGosCbUaB3Pwfw4R8tj1SjYlfG1i6K6c54LRdZSgvKWIYjNf8LFVcFndHROLWJ-UnBu0lBZAL8Co0avJfry2__z15cTdm3R-wWVBu23rUHq03B7ADq3nnfQ_0wOYLlre_vpyFvfS9H38eyV8dTfyi6Nzr9A2K3_Pc</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Kumar, Subaschandrabose Rajesh</creator><creator>Prabakaran, Mookkan</creator><creator>Ashok Raj, Kattur Venkatachalam</creator><creator>He, Fang</creator><creator>Kwang, Jimmy</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>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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150601</creationdate><title>Amino Acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge</title><author>Kumar, Subaschandrabose Rajesh ; Prabakaran, Mookkan ; Ashok Raj, Kattur Venkatachalam ; He, Fang ; Kwang, Jimmy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-e767616a90fcace9be1eece8b39dc8ed834d905189bbc8cd10ae5cec4750569b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Amino acid substitution</topic><topic>Amino Acid Substitution - 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Our previous vaccine study reported that mice when immunized intranasally (i.n) with live Bac-HA were protected from lethal H7N7/NL/219/03 challenge, whereas incomplete protection was obtained when administered subcutaneously (s.c) due to the fact that H7N7 is a poor inducer of neutralizing antibodies. Interestingly, our recent vaccine studies reported that mice when vaccinated subcutaneously with Bac-HA (H7N9) was protected against both H7N9 (A/Sh2/2013) and H7N7 virus challenge. HA1 region of both H7N7 and H7N9 viruses are differ at 15 amino acid positions. Among those, we selected three amino acid positions (T143, T198 and I211) in HA1 region of H7N7. These amino acids are located within or near the receptor binding site. Following the selection, we substituted the amino acid at these three positions with amino acids found on H7N9HA wild-type. In this study, we evaluate the impact of amino acid substitutions in the H7N7 HA-protein on the immunogenicity. We generated six mutant constructs from wild-type influenza H7N7HA cDNA by site directed mutagenesis, and individually expressed mutant HA protein on the surface of baculovirus (Bac-HAm) and compared their protective efficacy of the vaccines with Bac-H7N7HA wild-type (Bac-HA) by lethal H7N7 viral challenge in a mouse model. We found that mice immunized subcutaneously with Bac-HAm constructs T143A or T198A-I211V or I211V-T143A serum showed significantly higher hemagglutination inhibition and neutralization titer against H7N7 and H7N9 viruses when compared to Bac-HA vaccinated mice groups. We also observed low level of lung viral titer, negligible weight loss and complete protection against lethal H7N7 viral challenge. Our results indicated that amino acid substitution at position 143 or 211 improve immunogenicity of H7N7HA vaccine against H7N7/NL/219/03 virus.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26030920</pmid><doi>10.1371/journal.pone.0128940</doi><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1684995304 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Amino acid substitution Amino Acid Substitution - immunology Amino acids Animals Antibodies Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Antibody Formation - immunology Avian flu Avian influenza Baculovirus Binding sites Biotechnology Cell Line Cytotoxicity Female HA protein Health aspects Health risks Hemagglutination inhibition Immunization Immunization - methods Immunogenicity Influenza Influenza A Influenza A Virus, H7N7 Subtype - immunology Influenza A Virus, H7N9 Subtype - immunology Influenza Vaccines - immunology Low level Lungs Medical laboratories Mice Mice, Inbred BALB C Mutagenesis Neutralization Occupational accidents Orthomyxoviridae Infections - immunology Pandemics Peptides Proteins Sf9 Cells Site-directed mutagenesis Spodoptera Vaccination Vaccination - methods Vaccines Viruses |
| title | Amino Acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T10%3A16%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Amino%20Acid%20Substitutions%20Improve%20the%20Immunogenicity%20of%20H7N7HA%20Protein%20and%20Protect%20Mice%20against%20Lethal%20H7N7%20Viral%20Challenge&rft.jtitle=PloS%20one&rft.au=Kumar,%20Subaschandrabose%20Rajesh&rft.date=2015-06-01&rft.volume=10&rft.issue=6&rft.spage=e0128940&rft.pages=e0128940-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0128940&rft_dat=%3Cgale_plos_%3EA423835540%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1684995304&rft_id=info:pmid/26030920&rft_galeid=A423835540&rft_doaj_id=oai_doaj_org_article_2a25559a70014396a013e9213af6d597&rfr_iscdi=true |