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A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models
The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series o...
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Published in: | PloS one 2010-02, Vol.5 (2), p.e9349-e9349 |
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creator | Kistner, Otfried Crowe, Brian A Wodal, Walter Kerschbaum, Astrid Savidis-Dacho, Helga Sabarth, Nicolas Falkner, Falko G Mayerhofer, Ines Mundt, Wolfgang Reiter, Manfred Grillberger, Leopold Tauer, Christa Graninger, Michael Sachslehner, Alois Schwendinger, Michael Brühl, Peter Kreil, Thomas R Ehrlich, Hartmut J Barrett, P Noel |
description | The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID) mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus pandemic H1N1 and a split seasonal H1N1 vaccine were also compared in this study. It was demonstrated that the whole virus vaccine induced a balanced Th-1 and Th-2 response in mice, whereas the split vaccine induced mainly a Th-2 response and only minimal levels of Th-1 responses. These data supported the initiation of clinical studies with the same low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a whole virus H5N1 vaccine. |
doi_str_mv | 10.1371/journal.pone.0009349 |
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Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID) mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus pandemic H1N1 and a split seasonal H1N1 vaccine were also compared in this study. It was demonstrated that the whole virus vaccine induced a balanced Th-1 and Th-2 response in mice, whereas the split vaccine induced mainly a Th-2 response and only minimal levels of Th-1 responses. These data supported the initiation of clinical studies with the same low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a whole virus H5N1 vaccine.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0009349</identifier><identifier>PMID: 20186321</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject><![CDATA[Analysis ; Animal models ; Animals ; Antigens ; Antisera ; Avian flu ; Avian influenza ; Combined vaccines ; Disease Models, Animal ; Disease Outbreaks ; Helper cells ; Humans ; Illnesses ; Immune response ; Immune serum ; Immune system ; Immunization ; Immunodeficiency ; Immunogenicity ; Immunology ; Immunology/Immune Response ; Immunology/Immunity to Infections ; Influenza ; Influenza A Virus, H1N1 Subtype - immunology ; Influenza A Virus, H5N1 Subtype - immunology ; Influenza vaccines ; Influenza Vaccines - administration & dosage ; Influenza Vaccines - immunology ; Influenza viruses ; Influenza, Human - epidemiology ; Influenza, Human - immunology ; Influenza, Human - prevention & control ; Laboratory animals ; Livestock ; Lymphocytes T ; Medical laboratories ; Medical research ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Orthomyxoviridae Infections - immunology ; Orthomyxoviridae Infections - prevention & control ; Pandemics ; R&D ; Research & development ; Swine ; Swine - virology ; Swine flu ; Swine influenza ; Th1 Cells - immunology ; Th2 Cells - immunology ; Treatment Outcome ; Vaccination ; Vaccination - methods ; Vaccines ; Viral Vaccines - administration & dosage ; Viral Vaccines - immunology ; Viremia - immunology ; Viremia - prevention & control ; Virology ; Virology/New Therapies, including Antivirals and Immunotherapy ; Virology/Vaccines ; Viruses]]></subject><ispartof>PloS one, 2010-02, Vol.5 (2), p.e9349-e9349</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Kistner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Kistner et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-ee86b51f252ed35c52587079ed525d64aeacbb3d1de83fa8d67be6bcefd766aa3</citedby><cites>FETCH-LOGICAL-c757t-ee86b51f252ed35c52587079ed525d64aeacbb3d1de83fa8d67be6bcefd766aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1289259703/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1289259703?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20186321$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hasenkrug, Kim J.</contributor><creatorcontrib>Kistner, Otfried</creatorcontrib><creatorcontrib>Crowe, Brian A</creatorcontrib><creatorcontrib>Wodal, Walter</creatorcontrib><creatorcontrib>Kerschbaum, Astrid</creatorcontrib><creatorcontrib>Savidis-Dacho, Helga</creatorcontrib><creatorcontrib>Sabarth, Nicolas</creatorcontrib><creatorcontrib>Falkner, Falko G</creatorcontrib><creatorcontrib>Mayerhofer, Ines</creatorcontrib><creatorcontrib>Mundt, Wolfgang</creatorcontrib><creatorcontrib>Reiter, Manfred</creatorcontrib><creatorcontrib>Grillberger, Leopold</creatorcontrib><creatorcontrib>Tauer, Christa</creatorcontrib><creatorcontrib>Graninger, Michael</creatorcontrib><creatorcontrib>Sachslehner, Alois</creatorcontrib><creatorcontrib>Schwendinger, Michael</creatorcontrib><creatorcontrib>Brühl, Peter</creatorcontrib><creatorcontrib>Kreil, Thomas R</creatorcontrib><creatorcontrib>Ehrlich, Hartmut J</creatorcontrib><creatorcontrib>Barrett, P Noel</creatorcontrib><title>A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID) mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus pandemic H1N1 and a split seasonal H1N1 vaccine were also compared in this study. It was demonstrated that the whole virus vaccine induced a balanced Th-1 and Th-2 response in mice, whereas the split vaccine induced mainly a Th-2 response and only minimal levels of Th-1 responses. These data supported the initiation of clinical studies with the same low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a whole virus H5N1 vaccine.</description><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antigens</subject><subject>Antisera</subject><subject>Avian flu</subject><subject>Avian influenza</subject><subject>Combined vaccines</subject><subject>Disease Models, Animal</subject><subject>Disease Outbreaks</subject><subject>Helper cells</subject><subject>Humans</subject><subject>Illnesses</subject><subject>Immune response</subject><subject>Immune serum</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Immunodeficiency</subject><subject>Immunogenicity</subject><subject>Immunology</subject><subject>Immunology/Immune Response</subject><subject>Immunology/Immunity to Infections</subject><subject>Influenza</subject><subject>Influenza A Virus, H1N1 Subtype - immunology</subject><subject>Influenza A Virus, H5N1 Subtype - immunology</subject><subject>Influenza vaccines</subject><subject>Influenza Vaccines - administration & dosage</subject><subject>Influenza Vaccines - immunology</subject><subject>Influenza viruses</subject><subject>Influenza, Human - epidemiology</subject><subject>Influenza, Human - immunology</subject><subject>Influenza, Human - prevention & control</subject><subject>Laboratory animals</subject><subject>Livestock</subject><subject>Lymphocytes T</subject><subject>Medical laboratories</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, SCID</subject><subject>Orthomyxoviridae Infections - immunology</subject><subject>Orthomyxoviridae Infections - prevention & control</subject><subject>Pandemics</subject><subject>R&D</subject><subject>Research & development</subject><subject>Swine</subject><subject>Swine - virology</subject><subject>Swine flu</subject><subject>Swine influenza</subject><subject>Th1 Cells - immunology</subject><subject>Th2 Cells - immunology</subject><subject>Treatment Outcome</subject><subject>Vaccination</subject><subject>Vaccination - methods</subject><subject>Vaccines</subject><subject>Viral Vaccines - administration & dosage</subject><subject>Viral Vaccines - immunology</subject><subject>Viremia - immunology</subject><subject>Viremia - prevention & control</subject><subject>Virology</subject><subject>Virology/New Therapies, including Antivirals and 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whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models</title><author>Kistner, Otfried ; Crowe, Brian A ; Wodal, Walter ; Kerschbaum, Astrid ; Savidis-Dacho, Helga ; Sabarth, Nicolas ; Falkner, Falko G ; Mayerhofer, Ines ; Mundt, Wolfgang ; Reiter, Manfred ; Grillberger, Leopold ; Tauer, Christa ; Graninger, Michael ; Sachslehner, Alois ; Schwendinger, Michael ; Brühl, Peter ; Kreil, Thomas R ; Ehrlich, Hartmut J ; Barrett, P Noel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-ee86b51f252ed35c52587079ed525d64aeacbb3d1de83fa8d67be6bcefd766aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antigens</topic><topic>Antisera</topic><topic>Avian flu</topic><topic>Avian influenza</topic><topic>Combined 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Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kistner, Otfried</au><au>Crowe, Brian A</au><au>Wodal, Walter</au><au>Kerschbaum, Astrid</au><au>Savidis-Dacho, Helga</au><au>Sabarth, Nicolas</au><au>Falkner, Falko G</au><au>Mayerhofer, Ines</au><au>Mundt, Wolfgang</au><au>Reiter, Manfred</au><au>Grillberger, Leopold</au><au>Tauer, Christa</au><au>Graninger, Michael</au><au>Sachslehner, Alois</au><au>Schwendinger, Michael</au><au>Brühl, Peter</au><au>Kreil, Thomas R</au><au>Ehrlich, Hartmut J</au><au>Barrett, P Noel</au><au>Hasenkrug, Kim J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-02-23</date><risdate>2010</risdate><volume>5</volume><issue>2</issue><spage>e9349</spage><epage>e9349</epage><pages>e9349-e9349</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID) mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus pandemic H1N1 and a split seasonal H1N1 vaccine were also compared in this study. It was demonstrated that the whole virus vaccine induced a balanced Th-1 and Th-2 response in mice, whereas the split vaccine induced mainly a Th-2 response and only minimal levels of Th-1 responses. These data supported the initiation of clinical studies with the same low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a whole virus H5N1 vaccine.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20186321</pmid><doi>10.1371/journal.pone.0009349</doi><tpages>e9349</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2010-02, Vol.5 (2), p.e9349-e9349 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1289259703 |
source | Publicly Available Content Database; PubMed Central |
subjects | Analysis Animal models Animals Antigens Antisera Avian flu Avian influenza Combined vaccines Disease Models, Animal Disease Outbreaks Helper cells Humans Illnesses Immune response Immune serum Immune system Immunization Immunodeficiency Immunogenicity Immunology Immunology/Immune Response Immunology/Immunity to Infections Influenza Influenza A Virus, H1N1 Subtype - immunology Influenza A Virus, H5N1 Subtype - immunology Influenza vaccines Influenza Vaccines - administration & dosage Influenza Vaccines - immunology Influenza viruses Influenza, Human - epidemiology Influenza, Human - immunology Influenza, Human - prevention & control Laboratory animals Livestock Lymphocytes T Medical laboratories Medical research Mice Mice, Inbred BALB C Mice, SCID Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - prevention & control Pandemics R&D Research & development Swine Swine - virology Swine flu Swine influenza Th1 Cells - immunology Th2 Cells - immunology Treatment Outcome Vaccination Vaccination - methods Vaccines Viral Vaccines - administration & dosage Viral Vaccines - immunology Viremia - immunology Viremia - prevention & control Virology Virology/New Therapies, including Antivirals and Immunotherapy Virology/Vaccines Viruses |
title | A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models |
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