Preclinical efficacy studies of influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine
A universal influenza vaccine that does not require annual reformulation would have clear advantages over the currently approved seasonal vaccine. In this study, we combined the mucosal adjuvant alpha-galactosylceramide (αGalCer) and peptides designed across the highly conserved influenza precursor...
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Veröffentlicht in: | Journal of general virology 2011-05, Vol.92 (Pt 5), p.1152-1161 |
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creator | MILLER, Darren S FINNIE, John BOWDEN, Timothy R SCHOLZ, Anita C OH, Sawyin KOK, Tuckweng BURRELL, Christopher J TRINIDAD, Lee BOYLE, David B PENG LI |
description | A universal influenza vaccine that does not require annual reformulation would have clear advantages over the currently approved seasonal vaccine. In this study, we combined the mucosal adjuvant alpha-galactosylceramide (αGalCer) and peptides designed across the highly conserved influenza precursor haemagglutinin (HA(0)) cleavage loop as a vaccine. Peptides designed across the HA(0) of influenza A/H3N2 viruses, delivered to mice via the intranasal route with αGalCer as an adjuvant, provided 100 % protection following H3N2 virus challenge. Similarly, intranasal inoculation of peptides across the HA(0) of influenza A/H5N1 with αGalCer completely protected mice against heterotypic challenge with H3N2 virus. Our data suggest that these peptide vaccines effectively inhibited subsequent influenza A/H3N2 virus replication. In contrast, only 20 % of mice vaccinated with αGalCer-adjuvanted peptides spanning the HA(0) of H5N1 survived homologous viral challenge, possibly because the HA(0) of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA(0) peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine. |
doi_str_mv | 10.1099/vir.0.028985-0 |
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In this study, we combined the mucosal adjuvant alpha-galactosylceramide (αGalCer) and peptides designed across the highly conserved influenza precursor haemagglutinin (HA(0)) cleavage loop as a vaccine. Peptides designed across the HA(0) of influenza A/H3N2 viruses, delivered to mice via the intranasal route with αGalCer as an adjuvant, provided 100 % protection following H3N2 virus challenge. Similarly, intranasal inoculation of peptides across the HA(0) of influenza A/H5N1 with αGalCer completely protected mice against heterotypic challenge with H3N2 virus. Our data suggest that these peptide vaccines effectively inhibited subsequent influenza A/H3N2 virus replication. In contrast, only 20 % of mice vaccinated with αGalCer-adjuvanted peptides spanning the HA(0) of H5N1 survived homologous viral challenge, possibly because the HA(0) of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA(0) peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine.</description><identifier>ISSN: 0022-1317</identifier><identifier>EISSN: 1465-2099</identifier><identifier>DOI: 10.1099/vir.0.028985-0</identifier><identifier>PMID: 21289160</identifier><identifier>CODEN: JGVIAY</identifier><language>eng</language><publisher>Reading: Society for General Microbiology</publisher><subject><![CDATA[Adjuvants, Immunologic - administration & dosage ; Animals ; Biological and medical sciences ; Body Weight ; Cross Protection ; Female ; Fundamental and applied biological sciences. 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In this study, we combined the mucosal adjuvant alpha-galactosylceramide (αGalCer) and peptides designed across the highly conserved influenza precursor haemagglutinin (HA(0)) cleavage loop as a vaccine. Peptides designed across the HA(0) of influenza A/H3N2 viruses, delivered to mice via the intranasal route with αGalCer as an adjuvant, provided 100 % protection following H3N2 virus challenge. Similarly, intranasal inoculation of peptides across the HA(0) of influenza A/H5N1 with αGalCer completely protected mice against heterotypic challenge with H3N2 virus. Our data suggest that these peptide vaccines effectively inhibited subsequent influenza A/H3N2 virus replication. In contrast, only 20 % of mice vaccinated with αGalCer-adjuvanted peptides spanning the HA(0) of H5N1 survived homologous viral challenge, possibly because the HA(0) of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA(0) peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine.</description><subject>Adjuvants, Immunologic - administration & dosage</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Body Weight</subject><subject>Cross Protection</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Galactosylceramides - administration & dosage</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - immunology</subject><subject>Histocytochemistry</subject><subject>Influenza A Virus, H3N2 Subtype - genetics</subject><subject>Influenza A Virus, H3N2 Subtype - immunology</subject><subject>Influenza A Virus, H5N1 Subtype - genetics</subject><subject>Influenza A Virus, H5N1 Subtype - immunology</subject><subject>Influenza Vaccines - administration & dosage</subject><subject>Influenza Vaccines - immunology</subject><subject>Lung - pathology</subject><subject>Lung - virology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbiology</subject><subject>Microscopy</subject><subject>Miscellaneous</subject><subject>Orthomyxoviridae Infections - pathology</subject><subject>Orthomyxoviridae Infections - prevention & control</subject><subject>Protein Precursors - genetics</subject><subject>Protein Precursors - metabolism</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies</subject><subject>Vaccines, Subunit - administration & dosage</subject><subject>Vaccines, Subunit - immunology</subject><subject>Viral Load</subject><subject>Virology</subject><issn>0022-1317</issn><issn>1465-2099</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtPGzEURq0KVAJ022XlDWI16bXH8_AyilpAikQXsLZsz3XqypkZ7JlI4dfjKgEkS3fhc77FIeQ7gyUDKX_ufVzCEngr26qAL2TBRF0VPH-dkQUA5wUrWXNBLlP6B8CEqJqv5IKzLLAaFiT-iWiD773VgaJz-doDTdPceUx0cNT3LszYv2q6on817vR2G-YpCz0dszrHNERqA-q93iINwzDSEcfJd1nX-dFxmLCffJ7fa2t9j9fk3OmQ8NvpXpHn37-e1vfF5vHuYb3aFFaUMBUGQBoJwsmaG9MZ62ot0GDLnKyqrm1ACt045BJr0wnTyFI3FXdtV3bOgSmvyO1xd4zDy4xpUjufLIagexzmpNqa87apa57J5ZG0cUgpolNj9DsdD4qB-p9Z5cwK1DGzgiz8OE3PZofdB_7eNQM3J0CnXNZF3VufPjnBOBcgyjcbQoi-</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>MILLER, Darren S</creator><creator>FINNIE, John</creator><creator>BOWDEN, Timothy R</creator><creator>SCHOLZ, Anita C</creator><creator>OH, Sawyin</creator><creator>KOK, Tuckweng</creator><creator>BURRELL, Christopher J</creator><creator>TRINIDAD, Lee</creator><creator>BOYLE, David B</creator><creator>PENG LI</creator><general>Society for General Microbiology</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20110501</creationdate><title>Preclinical efficacy studies of influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine</title><author>MILLER, Darren S ; FINNIE, John ; BOWDEN, Timothy R ; SCHOLZ, Anita C ; OH, Sawyin ; KOK, Tuckweng ; BURRELL, Christopher J ; TRINIDAD, Lee ; BOYLE, David B ; PENG LI</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-b009b904f962bbdbcf6a4ebe81f955d87094a7fe29e6bd4b793a752f8d3dff0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adjuvants, Immunologic - administration & dosage</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Body Weight</topic><topic>Cross Protection</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Galactosylceramides - administration & dosage</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - immunology</topic><topic>Histocytochemistry</topic><topic>Influenza A Virus, H3N2 Subtype - genetics</topic><topic>Influenza A Virus, H3N2 Subtype - immunology</topic><topic>Influenza A Virus, H5N1 Subtype - genetics</topic><topic>Influenza A Virus, H5N1 Subtype - immunology</topic><topic>Influenza Vaccines - administration & dosage</topic><topic>Influenza Vaccines - immunology</topic><topic>Lung - pathology</topic><topic>Lung - virology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbiology</topic><topic>Microscopy</topic><topic>Miscellaneous</topic><topic>Orthomyxoviridae Infections - pathology</topic><topic>Orthomyxoviridae Infections - prevention & control</topic><topic>Protein Precursors - genetics</topic><topic>Protein Precursors - metabolism</topic><topic>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies</topic><topic>Vaccines, Subunit - administration & dosage</topic><topic>Vaccines, Subunit - immunology</topic><topic>Viral Load</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MILLER, Darren S</creatorcontrib><creatorcontrib>FINNIE, John</creatorcontrib><creatorcontrib>BOWDEN, Timothy R</creatorcontrib><creatorcontrib>SCHOLZ, Anita C</creatorcontrib><creatorcontrib>OH, Sawyin</creatorcontrib><creatorcontrib>KOK, Tuckweng</creatorcontrib><creatorcontrib>BURRELL, Christopher J</creatorcontrib><creatorcontrib>TRINIDAD, Lee</creatorcontrib><creatorcontrib>BOYLE, David B</creatorcontrib><creatorcontrib>PENG LI</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of general virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MILLER, Darren S</au><au>FINNIE, John</au><au>BOWDEN, Timothy R</au><au>SCHOLZ, Anita C</au><au>OH, Sawyin</au><au>KOK, Tuckweng</au><au>BURRELL, Christopher J</au><au>TRINIDAD, Lee</au><au>BOYLE, David B</au><au>PENG LI</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preclinical efficacy studies of influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine</atitle><jtitle>Journal of general virology</jtitle><addtitle>J Gen Virol</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>92</volume><issue>Pt 5</issue><spage>1152</spage><epage>1161</epage><pages>1152-1161</pages><issn>0022-1317</issn><eissn>1465-2099</eissn><coden>JGVIAY</coden><abstract>A universal influenza vaccine that does not require annual reformulation would have clear advantages over the currently approved seasonal vaccine. In this study, we combined the mucosal adjuvant alpha-galactosylceramide (αGalCer) and peptides designed across the highly conserved influenza precursor haemagglutinin (HA(0)) cleavage loop as a vaccine. Peptides designed across the HA(0) of influenza A/H3N2 viruses, delivered to mice via the intranasal route with αGalCer as an adjuvant, provided 100 % protection following H3N2 virus challenge. Similarly, intranasal inoculation of peptides across the HA(0) of influenza A/H5N1 with αGalCer completely protected mice against heterotypic challenge with H3N2 virus. Our data suggest that these peptide vaccines effectively inhibited subsequent influenza A/H3N2 virus replication. In contrast, only 20 % of mice vaccinated with αGalCer-adjuvanted peptides spanning the HA(0) of H5N1 survived homologous viral challenge, possibly because the HA(0) of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA(0) peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine.</abstract><cop>Reading</cop><pub>Society for General Microbiology</pub><pmid>21289160</pmid><doi>10.1099/vir.0.028985-0</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adjuvants, Immunologic - administration & dosage Animals Biological and medical sciences Body Weight Cross Protection Female Fundamental and applied biological sciences. Psychology Galactosylceramides - administration & dosage Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage Hemagglutinin Glycoproteins, Influenza Virus - immunology Histocytochemistry Influenza A Virus, H3N2 Subtype - genetics Influenza A Virus, H3N2 Subtype - immunology Influenza A Virus, H5N1 Subtype - genetics Influenza A Virus, H5N1 Subtype - immunology Influenza Vaccines - administration & dosage Influenza Vaccines - immunology Lung - pathology Lung - virology Mice Mice, Inbred BALB C Microbiology Microscopy Miscellaneous Orthomyxoviridae Infections - pathology Orthomyxoviridae Infections - prevention & control Protein Precursors - genetics Protein Precursors - metabolism Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies Vaccines, Subunit - administration & dosage Vaccines, Subunit - immunology Viral Load Virology |
title | Preclinical efficacy studies of influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine |
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