Microneedle vaccination with stabilized recombinant influenza virus hemagglutinin induces improved protective immunity.
Identifieur interne : 001119 ( PubMed/Corpus ); précédent : 001118; suivant : 001120Microneedle 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 [ 1556-679X ] ; 2011.
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.
DOI: 10.1128/CVI.00435-10
PubMed: 21288996
Links to Exploration step
pubmed:21288996Le document en format XML
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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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<Abstract><AbstractText>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.</AbstractText>
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