Microneedle Vaccination with Stabilized Recombinant Influenza Virus Hemagglutinin Induces Improved Protective Immunity ▿
Identifieur interne : 000675 ( Pmc/Corpus ); précédent : 000674; suivant : 000676Microneedle Vaccination with Stabilized Recombinant Influenza Virus Hemagglutinin Induces Improved Protective Immunity ▿
Auteurs : William C. Weldon ; Maria P. Martin ; Vladimir Zarnitsyn ; Baozhong Wang ; Dimitrios Koutsonanos ; Ioanna Skountzou ; Mark R. Prausnitz ; Richard W. CompansSource :
- Clinical and Vaccine Immunology : CVI [ 1556-6811 ] ; 2011.
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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<series><title level="j">Clinical and Vaccine Immunology : CVI</title>
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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>
</div>
</front>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Clin Vaccine Immunol</journal-id>
<journal-id journal-id-type="hwp">cdli</journal-id>
<journal-id journal-id-type="pmc">cvi</journal-id>
<journal-id journal-id-type="publisher-id">CVI</journal-id>
<journal-title-group><journal-title>Clinical and Vaccine Immunology : CVI</journal-title>
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<issn pub-type="ppub">1556-6811</issn>
<issn pub-type="epub">1556-679X</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21288996</article-id>
<article-id pub-id-type="pmc">3122571</article-id>
<article-id pub-id-type="publisher-id">0435-10</article-id>
<article-id pub-id-type="doi">10.1128/CVI.00435-10</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Vaccine Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Microneedle Vaccination with Stabilized Recombinant Influenza Virus Hemagglutinin Induces Improved Protective Immunity
<xref ref-type="fn" rid="FN1"><sup>▿</sup>
</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Weldon</surname>
<given-names>William C.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Martin</surname>
<given-names>Maria P.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zarnitsyn</surname>
<given-names>Vladimir</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Baozhong</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Koutsonanos</surname>
<given-names>Dimitrios</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Skountzou</surname>
<given-names>Ioanna</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Prausnitz</surname>
<given-names>Mark R.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Compans</surname>
<given-names>Richard W.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<aff id="aff1"><label>1</label>
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322</aff>
<aff id="aff2"><label>2</label>
Wallace Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address: <addr-line>Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322</addr-line>
. Phone: <phone>(404) 727-3531</phone>
. Fax: <fax>(404) 727-3295</fax>
. E-mail: <email>rcompan@emory.edu</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>4</month>
<year>2011</year>
</pub-date>
<volume>18</volume>
<issue>4</issue>
<fpage>647</fpage>
<lpage>654</lpage>
<history><date date-type="received"><day>7</day>
<month>10</month>
<year>2010</year>
</date>
<date date-type="rev-request"><day>5</day>
<month>1</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>23</day>
<month>1</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2011, American Society for Microbiology</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zcd00411000647.pdf"></self-uri>
<abstract><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>
</abstract>
</article-meta>
</front>
</pmc>
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