Microneedle Vaccination with Stabilized Recombinant Influenza Virus Hemagglutinin Induces Improved Protective Immunity ▿
Identifieur interne : 000F37 ( Ncbi/Merge ); précédent : 000F36; suivant : 000F38Microneedle Vaccination with Stabilized Recombinant Influenza Virus Hemagglutinin Induces Improved Protective Immunity ▿
Auteurs : William C. Weldon [États-Unis] ; Maria P. Martin [États-Unis] ; Vladimir Zarnitsyn [États-Unis] ; Baozhong Wang [États-Unis] ; Dimitrios Koutsonanos [États-Unis] ; Ioanna Skountzou [États-Unis] ; Mark R. Prausnitz [États-Unis] ; Richard W. Compans [États-Unis]Source :
- Clinical and Vaccine Immunology : CVI [ 1556-6811 ] ; 2011.
Descripteurs français
- KwdFr :
- Analyse de survie, Animaux, Charge virale, Glycoprotéine hémagglutinine du virus influenza (administration et posologie), Glycoprotéine hémagglutinine du virus influenza (immunologie), Immunité muqueuse, Infections à Orthomyxoviridae (), Infections à Orthomyxoviridae (immunologie), Injections intradermiques (), Lymphocytes auxiliaires Th1 (immunologie), Modèles animaux de maladie humaine, Poumon (virologie), Souris, Souris de lignée BALB C, Vaccination (), Vaccins antigrippaux (administration et posologie), Vaccins antigrippaux (immunologie), Vaccins sous-unitaires (administration et posologie), Vaccins sous-unitaires (immunologie), Vaccins synthétiques (administration et posologie), Vaccins synthétiques (immunologie), Virus de la grippe A (immunologie).
- MESH :
- administration et posologie : Glycoprotéine hémagglutinine du virus influenza, Vaccins antigrippaux, Vaccins sous-unitaires, Vaccins synthétiques.
- immunologie : Glycoprotéine hémagglutinine du virus influenza, Infections à Orthomyxoviridae, Lymphocytes auxiliaires Th1, Vaccins antigrippaux, Vaccins sous-unitaires, Vaccins synthétiques, Virus de la grippe A.
- virologie : Poumon.
- Analyse de survie, Animaux, Charge virale, Immunité muqueuse, Infections à Orthomyxoviridae, Injections intradermiques, Modèles animaux de maladie humaine, Souris, Souris de lignée BALB C, Vaccination.
English descriptors
- KwdEn :
- Animals, Disease Models, Animal, Hemagglutinin Glycoproteins, Influenza Virus (administration & dosage), Hemagglutinin Glycoproteins, Influenza Virus (immunology), Immunity, Mucosal, Influenza A virus (immunology), Influenza Vaccines (administration & dosage), Influenza Vaccines (immunology), Injections, Intradermal (methods), Lung (virology), Mice, Mice, Inbred BALB C, Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (prevention & control), Survival Analysis, Th1 Cells (immunology), Vaccination (methods), Vaccines, Subunit (administration & dosage), Vaccines, Subunit (immunology), Vaccines, Synthetic (administration & dosage), Vaccines, Synthetic (immunology), Viral Load.
- MESH :
- chemical , administration & dosage : Hemagglutinin Glycoproteins, Influenza Virus, Influenza Vaccines, Vaccines, Subunit, Vaccines, Synthetic.
- chemical , immunology : Hemagglutinin Glycoproteins, Influenza Virus, Influenza Vaccines, Vaccines, Subunit, Vaccines, Synthetic.
- immunology : Influenza A virus, Orthomyxoviridae Infections, Th1 Cells.
- methods : Injections, Intradermal, Vaccination.
- prevention & control : Orthomyxoviridae Infections.
- virology : Lung.
- Animals, Disease Models, Animal, Immunity, Mucosal, Mice, Mice, Inbred BALB C, Survival Analysis, Viral Load.
Abstract
The emergence of the swine-origin 2009 influenza pandemic illustrates the need for improved vaccine production and delivery strategies. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. Microneedles (MNs) can deliver vaccine to the epidermis and dermis, which are rich in antigen-presenting cells (APC) such as Langerhans cells and dermal dendritic cells. Previous studies using coated or dissolvable microneedles emphasized the use of inactivated influenza virus or virus-like particles as skin-based vaccines. However, most currently available influenza vaccines consist of solubilized viral protein antigens. Here we test the hypothesis that a recombinant subunit influenza vaccine can be delivered to the skin by coated microneedles and can induce protective immunity. We found that mice vaccinated via MN delivery with a stabilized recombinant trimeric soluble hemagglutinin (sHA) derived from A/Aichi/2/68 (H3) virus had significantly higher immune responses than did mice vaccinated with unmodified sHA. These mice were fully protected against a lethal challenge with influenza virus. Analysis of postchallenge lung titers showed that MN-immunized mice had completely cleared the virus from their lungs, in contrast to mice given the same vaccine by a standard subcutaneous route. In addition, we observed a higher ratio of antigen-specific Th1 cells in trimeric sHA-vaccinated mice and a greater mucosal antibody response. Our data therefore demonstrate the improved efficacy of a skin-based recombinant subunit influenza vaccine and emphasize the advantage of this route of vaccination for a protein subunit vaccine.
Url:
DOI: 10.1128/CVI.00435-10
PubMed: 21288996
PubMed Central: 3122571
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PMC:3122571Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>The emergence of the swine-origin 2009 influenza pandemic illustrates the need for improved vaccine production and delivery strategies. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. Microneedles (MNs) can deliver vaccine to the epidermis and dermis, which are rich in antigen-presenting cells (APC) such as Langerhans cells and dermal dendritic cells. Previous studies using coated or dissolvable microneedles emphasized the use of inactivated influenza virus or virus-like particles as skin-based vaccines. However, most currently available influenza vaccines consist of solubilized viral protein antigens. Here we test the hypothesis that a recombinant subunit influenza vaccine can be delivered to the skin by coated microneedles and can induce protective immunity. We found that mice vaccinated via MN delivery with a stabilized recombinant trimeric soluble hemagglutinin (sHA) derived from A/Aichi/2/68 (H3) virus had significantly higher immune responses than did mice vaccinated with unmodified sHA. These mice were fully protected against a lethal challenge with influenza virus. Analysis of postchallenge lung titers showed that MN-immunized mice had completely cleared the virus from their lungs, in contrast to mice given the same vaccine by a standard subcutaneous route. In addition, we observed a higher ratio of antigen-specific Th1 cells in trimeric sHA-vaccinated mice and a greater mucosal antibody response. Our data therefore demonstrate the improved efficacy of a skin-based recombinant subunit influenza vaccine and emphasize the advantage of this route of vaccination for a protein subunit vaccine.</p>
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<double pmid="21288996"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Microneedle Vaccination with Stabilized Recombinant Influenza Virus Hemagglutinin Induces Improved Protective Immunity
<xref ref-type="fn" rid="FN1"><sup>▿</sup>
</xref>
</title>
<author><name sortKey="Weldon, William C" sort="Weldon, William C" uniqKey="Weldon W" first="William C." last="Weldon">William C. Weldon</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta</wicri:cityArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Microneedle Vaccination with Stabilized Recombinant Influenza Virus Hemagglutinin Induces Improved Protective Immunity
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</xref>
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<author><name sortKey="Weldon, William C" sort="Weldon, William C" uniqKey="Weldon W" first="William C." last="Weldon">William C. Weldon</name>
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<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta</wicri:cityArea>
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<author><name sortKey="Martin, Maria P" sort="Martin, Maria P" uniqKey="Martin M" first="Maria P." last="Martin">Maria P. Martin</name>
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<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Wallace Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta</wicri:cityArea>
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<author><name sortKey="Wang, Baozhong" sort="Wang, Baozhong" uniqKey="Wang B" first="Baozhong" last="Wang">Baozhong Wang</name>
<affiliation wicri:level="2"><nlm:aff id="aff1">Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Koutsonanos, Dimitrios" sort="Koutsonanos, Dimitrios" uniqKey="Koutsonanos D" first="Dimitrios" last="Koutsonanos">Dimitrios Koutsonanos</name>
<affiliation wicri:level="2"><nlm:aff id="aff1">Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Skountzou, Ioanna" sort="Skountzou, Ioanna" uniqKey="Skountzou I" first="Ioanna" last="Skountzou">Ioanna Skountzou</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
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<wicri:cityArea>Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta</wicri:cityArea>
</affiliation>
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<author><name sortKey="Prausnitz, Mark R" sort="Prausnitz, Mark R" uniqKey="Prausnitz M" first="Mark R." last="Prausnitz">Mark R. Prausnitz</name>
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<placeName><region type="state">Géorgie (États-Unis)</region>
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<front><div type="abstract" xml:lang="en"><p>The emergence of the swine-origin 2009 influenza pandemic illustrates the need for improved vaccine production and delivery strategies. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. Microneedles (MNs) can deliver vaccine to the epidermis and dermis, which are rich in antigen-presenting cells (APC) such as Langerhans cells and dermal dendritic cells. Previous studies using coated or dissolvable microneedles emphasized the use of inactivated influenza virus or virus-like particles as skin-based vaccines. However, most currently available influenza vaccines consist of solubilized viral protein antigens. Here we test the hypothesis that a recombinant subunit influenza vaccine can be delivered to the skin by coated microneedles and can induce protective immunity. We found that mice vaccinated via MN delivery with a stabilized recombinant trimeric soluble hemagglutinin (sHA) derived from A/Aichi/2/68 (H3) virus had significantly higher immune responses than did mice vaccinated with unmodified sHA. These mice were fully protected against a lethal challenge with influenza virus. Analysis of postchallenge lung titers showed that MN-immunized mice had completely cleared the virus from their lungs, in contrast to mice given the same vaccine by a standard subcutaneous route. In addition, we observed a higher ratio of antigen-specific Th1 cells in trimeric sHA-vaccinated mice and a greater mucosal antibody response. Our data therefore demonstrate the improved efficacy of a skin-based recombinant subunit influenza vaccine and emphasize the advantage of this route of vaccination for a protein subunit vaccine.</p>
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<term>Immunity, Mucosal</term>
<term>Influenza A virus (immunology)</term>
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<term>Influenza Vaccines (immunology)</term>
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<term>Glycoprotéine hémagglutinine du virus influenza (immunologie)</term>
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<term>Infections à Orthomyxoviridae (immunologie)</term>
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<front><div type="abstract" xml:lang="en">The emergence of the swine-origin 2009 influenza pandemic illustrates the need for improved vaccine production and delivery strategies. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. Microneedles (MNs) can deliver vaccine to the epidermis and dermis, which are rich in antigen-presenting cells (APC) such as Langerhans cells and dermal dendritic cells. Previous studies using coated or dissolvable microneedles emphasized the use of inactivated influenza virus or virus-like particles as skin-based vaccines. However, most currently available influenza vaccines consist of solubilized viral protein antigens. Here we test the hypothesis that a recombinant subunit influenza vaccine can be delivered to the skin by coated microneedles and can induce protective immunity. We found that mice vaccinated via MN delivery with a stabilized recombinant trimeric soluble hemagglutinin (sHA) derived from A/Aichi/2/68 (H3) virus had significantly higher immune responses than did mice vaccinated with unmodified sHA. These mice were fully protected against a lethal challenge with influenza virus. Analysis of postchallenge lung titers showed that MN-immunized mice had completely cleared the virus from their lungs, in contrast to mice given the same vaccine by a standard subcutaneous route. In addition, we observed a higher ratio of antigen-specific Th1 cells in trimeric sHA-vaccinated mice and a greater mucosal antibody response. Our data therefore demonstrate the improved efficacy of a skin-based recombinant subunit influenza vaccine and emphasize the advantage of this route of vaccination for a protein subunit vaccine.</div>
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