Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine

Abstract The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of m...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Vaccine 2015-12, Vol.33 (51), p.7245-7253
Hauptverfasser: Carignan, Damien, Thérien, Ariane, Rioux, Gervais, Paquet, Geneviève, Gagné, Marie-Ève Laliberté, Bolduc, Marilène, Savard, Pierre, Leclerc, Denis
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 7253
container_issue 51
container_start_page 7245
container_title Vaccine
container_volume 33
creator Carignan, Damien
Thérien, Ariane
Rioux, Gervais
Paquet, Geneviève
Gagné, Marie-Ève Laliberté
Bolduc, Marilène
Savard, Pierre
Leclerc, Denis
description Abstract The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6–14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus-like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti-M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine.
doi_str_mv 10.1016/j.vaccine.2015.10.123
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1751228675</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0264410X15015790</els_id><sourcerecordid>1750426999</sourcerecordid><originalsourceid>FETCH-LOGICAL-c481t-29b6c536410c9e0199225f103795c06242f33dc2ad430b5f4ab6ccbb944345883</originalsourceid><addsrcrecordid>eNqNkltrFDEUgIModq3-BCXgiy-z5j6TF0VKrUKLghd8C9nMmW7W2WSazGxpf70Zd6vQF30KnHznO5wLQs8pWVJC1evNcmed8wGWjFC5nMOMP0AL2tS8YpI2D9GCMCUqQcmPI_Qk5w0hRHKqH6MjpqTQXLEFuj4Nl0UCyYdLHDs8rgF_tsPFd3zQ46G3YxfTFl_7cY0tzuuYRgjQ4gtWfmEYfQu4B9tmPEZsA4auAzf6HeBY8tuYAfvQ9ROEW3unfYoedbbP8OzwHqNv70-_nnyozj-dfTx5d1450dCxYnqlnOSqNOE0EKo1Y7KjhNdaOqKYYB3nrWO2FZysZCds4d1qpYXgQjYNP0av9t4hxasJ8mi2PjvoexsgTtnQWlLGGlXL_0GJYEprXdCX99BNnFIojRRKKNnUlNWFknvKpZhzgs4MyW9tujGUmHmJZmMO4zDzEn-HGS95Lw72abWF9k_W3dYK8HYPQJnczkMy2XkIDlqfyuRNG_0_S7y5Z3C9D97Z_ifcQP7bjcnMEPNlvqT5kKgskloT_guQYsNK</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1746587127</pqid></control><display><type>article</type><title>Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><source>ProQuest Central UK/Ireland</source><creator>Carignan, Damien ; Thérien, Ariane ; Rioux, Gervais ; Paquet, Geneviève ; Gagné, Marie-Ève Laliberté ; Bolduc, Marilène ; Savard, Pierre ; Leclerc, Denis</creator><creatorcontrib>Carignan, Damien ; Thérien, Ariane ; Rioux, Gervais ; Paquet, Geneviève ; Gagné, Marie-Ève Laliberté ; Bolduc, Marilène ; Savard, Pierre ; Leclerc, Denis</creatorcontrib><description>Abstract The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6–14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus-like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti-M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2015.10.123</identifier><identifier>PMID: 26549362</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Alphaflexiviridae ; Amino acids ; Animals ; Antibodies, Viral - blood ; Antigens ; Capsid Proteins - genetics ; Cytotoxicity ; Disease Models, Animal ; Dose-Response Relationship, Immunologic ; Drug Carriers ; E coli ; Epidemics ; Immunization ; Immunogenicity ; Immunoglobulin G - blood ; Immunoglobulins ; Infections ; Influenza ; Influenza Vaccines - administration &amp; dosage ; Influenza Vaccines - genetics ; Influenza Vaccines - immunology ; Influenza virus ; Injections, Intramuscular ; M2e ; Matrix protein 2 ; Mice, Inbred BALB C ; Molecular weight ; Morbidity ; Mortality ; Nanoparticles ; Orthomyxoviridae ; Orthomyxoviridae Infections - pathology ; Orthomyxoviridae Infections - prevention &amp; control ; Pandemics ; Papaya mosaic virus ; PapMV ; Peptides ; Potexvirus - genetics ; Proteins ; Public health ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - immunology ; Survival Analysis ; Vaccine ; Vaccines ; Vaccines, Synthetic - administration &amp; dosage ; Vaccines, Synthetic - genetics ; Vaccines, Synthetic - immunology ; Vaccines, Virus-Like Particle - administration &amp; dosage ; Vaccines, Virus-Like Particle - genetics ; Vaccines, Virus-Like Particle - immunology ; Viral Matrix Proteins - genetics ; Viral Matrix Proteins - immunology</subject><ispartof>Vaccine, 2015-12, Vol.33 (51), p.7245-7253</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Dec 16, 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-29b6c536410c9e0199225f103795c06242f33dc2ad430b5f4ab6ccbb944345883</citedby><cites>FETCH-LOGICAL-c481t-29b6c536410c9e0199225f103795c06242f33dc2ad430b5f4ab6ccbb944345883</cites><orcidid>0000-0001-7719-2811 ; 0000-0002-9323-1638</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1746587127?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26549362$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carignan, Damien</creatorcontrib><creatorcontrib>Thérien, Ariane</creatorcontrib><creatorcontrib>Rioux, Gervais</creatorcontrib><creatorcontrib>Paquet, Geneviève</creatorcontrib><creatorcontrib>Gagné, Marie-Ève Laliberté</creatorcontrib><creatorcontrib>Bolduc, Marilène</creatorcontrib><creatorcontrib>Savard, Pierre</creatorcontrib><creatorcontrib>Leclerc, Denis</creatorcontrib><title>Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6–14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus-like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti-M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine.</description><subject>Allergy and Immunology</subject><subject>Alphaflexiviridae</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antibodies, Viral - blood</subject><subject>Antigens</subject><subject>Capsid Proteins - genetics</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>Drug Carriers</subject><subject>E coli</subject><subject>Epidemics</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulins</subject><subject>Infections</subject><subject>Influenza</subject><subject>Influenza Vaccines - administration &amp; dosage</subject><subject>Influenza Vaccines - genetics</subject><subject>Influenza Vaccines - immunology</subject><subject>Influenza virus</subject><subject>Injections, Intramuscular</subject><subject>M2e</subject><subject>Matrix protein 2</subject><subject>Mice, Inbred BALB C</subject><subject>Molecular weight</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Nanoparticles</subject><subject>Orthomyxoviridae</subject><subject>Orthomyxoviridae Infections - pathology</subject><subject>Orthomyxoviridae Infections - prevention &amp; control</subject><subject>Pandemics</subject><subject>Papaya mosaic virus</subject><subject>PapMV</subject><subject>Peptides</subject><subject>Potexvirus - genetics</subject><subject>Proteins</subject><subject>Public health</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Survival Analysis</subject><subject>Vaccine</subject><subject>Vaccines</subject><subject>Vaccines, Synthetic - administration &amp; dosage</subject><subject>Vaccines, Synthetic - genetics</subject><subject>Vaccines, Synthetic - immunology</subject><subject>Vaccines, Virus-Like Particle - administration &amp; dosage</subject><subject>Vaccines, Virus-Like Particle - genetics</subject><subject>Vaccines, Virus-Like Particle - immunology</subject><subject>Viral Matrix Proteins - genetics</subject><subject>Viral Matrix Proteins - immunology</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkltrFDEUgIModq3-BCXgiy-z5j6TF0VKrUKLghd8C9nMmW7W2WSazGxpf70Zd6vQF30KnHznO5wLQs8pWVJC1evNcmed8wGWjFC5nMOMP0AL2tS8YpI2D9GCMCUqQcmPI_Qk5w0hRHKqH6MjpqTQXLEFuj4Nl0UCyYdLHDs8rgF_tsPFd3zQ46G3YxfTFl_7cY0tzuuYRgjQ4gtWfmEYfQu4B9tmPEZsA4auAzf6HeBY8tuYAfvQ9ROEW3unfYoedbbP8OzwHqNv70-_nnyozj-dfTx5d1450dCxYnqlnOSqNOE0EKo1Y7KjhNdaOqKYYB3nrWO2FZysZCds4d1qpYXgQjYNP0av9t4hxasJ8mi2PjvoexsgTtnQWlLGGlXL_0GJYEprXdCX99BNnFIojRRKKNnUlNWFknvKpZhzgs4MyW9tujGUmHmJZmMO4zDzEn-HGS95Lw72abWF9k_W3dYK8HYPQJnczkMy2XkIDlqfyuRNG_0_S7y5Z3C9D97Z_ifcQP7bjcnMEPNlvqT5kKgskloT_guQYsNK</recordid><startdate>20151216</startdate><enddate>20151216</enddate><creator>Carignan, Damien</creator><creator>Thérien, Ariane</creator><creator>Rioux, Gervais</creator><creator>Paquet, Geneviève</creator><creator>Gagné, Marie-Ève Laliberté</creator><creator>Bolduc, Marilène</creator><creator>Savard, Pierre</creator><creator>Leclerc, Denis</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>7U2</scope><orcidid>https://orcid.org/0000-0001-7719-2811</orcidid><orcidid>https://orcid.org/0000-0002-9323-1638</orcidid></search><sort><creationdate>20151216</creationdate><title>Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine</title><author>Carignan, Damien ; Thérien, Ariane ; Rioux, Gervais ; Paquet, Geneviève ; Gagné, Marie-Ève Laliberté ; Bolduc, Marilène ; Savard, Pierre ; Leclerc, Denis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-29b6c536410c9e0199225f103795c06242f33dc2ad430b5f4ab6ccbb944345883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Allergy and Immunology</topic><topic>Alphaflexiviridae</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Antibodies, Viral - blood</topic><topic>Antigens</topic><topic>Capsid Proteins - genetics</topic><topic>Cytotoxicity</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Immunologic</topic><topic>Drug Carriers</topic><topic>E coli</topic><topic>Epidemics</topic><topic>Immunization</topic><topic>Immunogenicity</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulins</topic><topic>Infections</topic><topic>Influenza</topic><topic>Influenza Vaccines - administration &amp; dosage</topic><topic>Influenza Vaccines - genetics</topic><topic>Influenza Vaccines - immunology</topic><topic>Influenza virus</topic><topic>Injections, Intramuscular</topic><topic>M2e</topic><topic>Matrix protein 2</topic><topic>Mice, Inbred BALB C</topic><topic>Molecular weight</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Nanoparticles</topic><topic>Orthomyxoviridae</topic><topic>Orthomyxoviridae Infections - pathology</topic><topic>Orthomyxoviridae Infections - prevention &amp; control</topic><topic>Pandemics</topic><topic>Papaya mosaic virus</topic><topic>PapMV</topic><topic>Peptides</topic><topic>Potexvirus - genetics</topic><topic>Proteins</topic><topic>Public health</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Survival Analysis</topic><topic>Vaccine</topic><topic>Vaccines</topic><topic>Vaccines, Synthetic - administration &amp; dosage</topic><topic>Vaccines, Synthetic - genetics</topic><topic>Vaccines, Synthetic - immunology</topic><topic>Vaccines, Virus-Like Particle - administration &amp; dosage</topic><topic>Vaccines, Virus-Like Particle - genetics</topic><topic>Vaccines, Virus-Like Particle - immunology</topic><topic>Viral Matrix Proteins - genetics</topic><topic>Viral Matrix Proteins - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carignan, Damien</creatorcontrib><creatorcontrib>Thérien, Ariane</creatorcontrib><creatorcontrib>Rioux, Gervais</creatorcontrib><creatorcontrib>Paquet, Geneviève</creatorcontrib><creatorcontrib>Gagné, Marie-Ève Laliberté</creatorcontrib><creatorcontrib>Bolduc, Marilène</creatorcontrib><creatorcontrib>Savard, Pierre</creatorcontrib><creatorcontrib>Leclerc, Denis</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech 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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Safety Science and Risk</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carignan, Damien</au><au>Thérien, Ariane</au><au>Rioux, Gervais</au><au>Paquet, Geneviève</au><au>Gagné, Marie-Ève Laliberté</au><au>Bolduc, Marilène</au><au>Savard, Pierre</au><au>Leclerc, Denis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2015-12-16</date><risdate>2015</risdate><volume>33</volume><issue>51</issue><spage>7245</spage><epage>7253</epage><pages>7245-7253</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>Abstract The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6–14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus-like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti-M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>26549362</pmid><doi>10.1016/j.vaccine.2015.10.123</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-7719-2811</orcidid><orcidid>https://orcid.org/0000-0002-9323-1638</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 0264-410X
ispartof Vaccine, 2015-12, Vol.33 (51), p.7245-7253
issn 0264-410X
1873-2518
language eng
recordid cdi_proquest_miscellaneous_1751228675
source MEDLINE; Elsevier ScienceDirect Journals Complete; ProQuest Central UK/Ireland
subjects Allergy and Immunology
Alphaflexiviridae
Amino acids
Animals
Antibodies, Viral - blood
Antigens
Capsid Proteins - genetics
Cytotoxicity
Disease Models, Animal
Dose-Response Relationship, Immunologic
Drug Carriers
E coli
Epidemics
Immunization
Immunogenicity
Immunoglobulin G - blood
Immunoglobulins
Infections
Influenza
Influenza Vaccines - administration & dosage
Influenza Vaccines - genetics
Influenza Vaccines - immunology
Influenza virus
Injections, Intramuscular
M2e
Matrix protein 2
Mice, Inbred BALB C
Molecular weight
Morbidity
Mortality
Nanoparticles
Orthomyxoviridae
Orthomyxoviridae Infections - pathology
Orthomyxoviridae Infections - prevention & control
Pandemics
Papaya mosaic virus
PapMV
Peptides
Potexvirus - genetics
Proteins
Public health
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - immunology
Survival Analysis
Vaccine
Vaccines
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - genetics
Vaccines, Synthetic - immunology
Vaccines, Virus-Like Particle - administration & dosage
Vaccines, Virus-Like Particle - genetics
Vaccines, Virus-Like Particle - immunology
Viral Matrix Proteins - genetics
Viral Matrix Proteins - immunology
title Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T07%3A43%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Engineering%20of%20the%20PapMV%20vaccine%20platform%20with%20a%20shortened%20M2e%20peptide%20leads%20to%20an%20effective%20one%20dose%20influenza%20vaccine&rft.jtitle=Vaccine&rft.au=Carignan,%20Damien&rft.date=2015-12-16&rft.volume=33&rft.issue=51&rft.spage=7245&rft.epage=7253&rft.pages=7245-7253&rft.issn=0264-410X&rft.eissn=1873-2518&rft_id=info:doi/10.1016/j.vaccine.2015.10.123&rft_dat=%3Cproquest_cross%3E1750426999%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1746587127&rft_id=info:pmid/26549362&rft_els_id=1_s2_0_S0264410X15015790&rfr_iscdi=true