A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets
There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP) as a ne...
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| description | There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP) as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1). In this study, a seasonal trivalent VLP vaccine (TVV) formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI) antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV). Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge. |
| doi_str_mv | 10.1371/journal.pone.0006032 |
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We have engineered an influenza virus-like particle (VLP) as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1). In this study, a seasonal trivalent VLP vaccine (TVV) formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI) antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV). Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0006032</identifier><identifier>PMID: 19554101</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adults ; Animals ; Antibodies ; Antigenic drift ; Antigens ; Avian flu ; CD8 antigen ; Cloning ; Cytokines ; Cytotoxicity ; Exo-a-sialidase ; Female ; Ferrets - immunology ; Genetic Engineering - methods ; Health aspects ; Health risks ; Hemagglutination ; Hemagglutination Tests ; Hemagglutinins ; Homology ; Humans ; Immune response ; Immunity ; Immunity, Cellular ; Immunization ; Immunoglobulins ; Immunology/Immune Response ; Infections ; Infectious Diseases/Respiratory Infections ; Influenza ; Influenza A ; Influenza A Virus, H1N1 Subtype - immunology ; Influenza A Virus, H3N2 Subtype - immunology ; Influenza B ; Influenza B virus - immunology ; Influenza vaccines ; Insect cells ; Insects ; Lectins ; Lymphocytes ; Lymphocytes T ; Male ; Medical research ; Mice ; Older people ; Orthomyxoviridae - immunology ; Proteins ; Replicating ; Replication ; Seasons ; Species Specificity ; Strains (organisms) ; Surveillance ; Swine influenza ; T cells ; Vaccination ; Vaccines ; Vaccines, Inactivated - immunology ; Vaccines, Virus-Like Particle - genetics ; Vaccines, Virus-Like Particle - immunology ; Viral proteins ; Viral Proteins - genetics ; Virology/Vaccines ; Viruses</subject><ispartof>PloS one, 2009-06, Vol.4 (6), p.e6032-e6032</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Ross et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (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>Ross et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c663t-3c1fcca94184154ddbca8de5a10bcdfeac566dd3ae31832801970eb67d6f9d143</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698286/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698286/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19554101$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Liu, Ding Xiang</contributor><creatorcontrib>Ross, Ted M</creatorcontrib><creatorcontrib>Mahmood, Kutub</creatorcontrib><creatorcontrib>Crevar, Corey J</creatorcontrib><creatorcontrib>Schneider-Ohrum, Kirsten</creatorcontrib><creatorcontrib>Heaton, Penny M</creatorcontrib><creatorcontrib>Bright, Rick A</creatorcontrib><title>A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP) as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1). In this study, a seasonal trivalent VLP vaccine (TVV) formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI) antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV). Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge.</description><subject>Adults</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigenic drift</subject><subject>Antigens</subject><subject>Avian flu</subject><subject>CD8 antigen</subject><subject>Cloning</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Exo-a-sialidase</subject><subject>Female</subject><subject>Ferrets - immunology</subject><subject>Genetic Engineering - methods</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Hemagglutination</subject><subject>Hemagglutination Tests</subject><subject>Hemagglutinins</subject><subject>Homology</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunity</subject><subject>Immunity, Cellular</subject><subject>Immunization</subject><subject>Immunoglobulins</subject><subject>Immunology/Immune Response</subject><subject>Infections</subject><subject>Infectious Diseases/Respiratory Infections</subject><subject>Influenza</subject><subject>Influenza A</subject><subject>Influenza A Virus, H1N1 Subtype - immunology</subject><subject>Influenza A Virus, H3N2 Subtype - immunology</subject><subject>Influenza B</subject><subject>Influenza B virus - immunology</subject><subject>Influenza vaccines</subject><subject>Insect cells</subject><subject>Insects</subject><subject>Lectins</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medical research</subject><subject>Mice</subject><subject>Older people</subject><subject>Orthomyxoviridae - immunology</subject><subject>Proteins</subject><subject>Replicating</subject><subject>Replication</subject><subject>Seasons</subject><subject>Species Specificity</subject><subject>Strains (organisms)</subject><subject>Surveillance</subject><subject>Swine influenza</subject><subject>T cells</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vaccines, Inactivated - immunology</subject><subject>Vaccines, Virus-Like Particle - genetics</subject><subject>Vaccines, Virus-Like Particle - immunology</subject><subject>Viral proteins</subject><subject>Viral Proteins - 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immunology</topic><topic>Genetic Engineering - methods</topic><topic>Health aspects</topic><topic>Health risks</topic><topic>Hemagglutination</topic><topic>Hemagglutination Tests</topic><topic>Hemagglutinins</topic><topic>Homology</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunity</topic><topic>Immunity, Cellular</topic><topic>Immunization</topic><topic>Immunoglobulins</topic><topic>Immunology/Immune Response</topic><topic>Infections</topic><topic>Infectious Diseases/Respiratory Infections</topic><topic>Influenza</topic><topic>Influenza A</topic><topic>Influenza A Virus, H1N1 Subtype - immunology</topic><topic>Influenza A Virus, H3N2 Subtype - immunology</topic><topic>Influenza B</topic><topic>Influenza B virus - immunology</topic><topic>Influenza vaccines</topic><topic>Insect cells</topic><topic>Insects</topic><topic>Lectins</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medical research</topic><topic>Mice</topic><topic>Older people</topic><topic>Orthomyxoviridae - 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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>Ross, Ted M</au><au>Mahmood, Kutub</au><au>Crevar, Corey J</au><au>Schneider-Ohrum, Kirsten</au><au>Heaton, Penny M</au><au>Bright, Rick A</au><au>Liu, Ding Xiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-06-24</date><risdate>2009</risdate><volume>4</volume><issue>6</issue><spage>e6032</spage><epage>e6032</epage><pages>e6032-e6032</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP) as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1). In this study, a seasonal trivalent VLP vaccine (TVV) formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI) antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV). Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19554101</pmid><doi>10.1371/journal.pone.0006032</doi><tpages>e6032</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2009-06, Vol.4 (6), p.e6032-e6032 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adults Animals Antibodies Antigenic drift Antigens Avian flu CD8 antigen Cloning Cytokines Cytotoxicity Exo-a-sialidase Female Ferrets - immunology Genetic Engineering - methods Health aspects Health risks Hemagglutination Hemagglutination Tests Hemagglutinins Homology Humans Immune response Immunity Immunity, Cellular Immunization Immunoglobulins Immunology/Immune Response Infections Infectious Diseases/Respiratory Infections Influenza Influenza A Influenza A Virus, H1N1 Subtype - immunology Influenza A Virus, H3N2 Subtype - immunology Influenza B Influenza B virus - immunology Influenza vaccines Insect cells Insects Lectins Lymphocytes Lymphocytes T Male Medical research Mice Older people Orthomyxoviridae - immunology Proteins Replicating Replication Seasons Species Specificity Strains (organisms) Surveillance Swine influenza T cells Vaccination Vaccines Vaccines, Inactivated - immunology Vaccines, Virus-Like Particle - genetics Vaccines, Virus-Like Particle - immunology Viral proteins Viral Proteins - genetics Virology/Vaccines Viruses |
| title | A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T04%3A32%3A02IST&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=A%20trivalent%20virus-like%20particle%20vaccine%20elicits%20protective%20immune%20responses%20against%20seasonal%20influenza%20strains%20in%20mice%20and%20ferrets&rft.jtitle=PloS%20one&rft.au=Ross,%20Ted%20M&rft.date=2009-06-24&rft.volume=4&rft.issue=6&rft.spage=e6032&rft.epage=e6032&rft.pages=e6032-e6032&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0006032&rft_dat=%3Cgale_plos_%3EA473032372%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=1289177180&rft_id=info:pmid/19554101&rft_galeid=A473032372&rft_doaj_id=oai_doaj_org_article_14af2c4438a44b5289d0c01d2e0f754c&rfr_iscdi=true |