A new adjuvanted nanoparticle-based H1N1 influenza vaccine induced antigen-specific local mucosal and systemic immune responses after administration into the lung.

2.50
Hdl Handle:
http://hdl.handle.net/10033/322187
Title:
A new adjuvanted nanoparticle-based H1N1 influenza vaccine induced antigen-specific local mucosal and systemic immune responses after administration into the lung.
Authors:
Neuhaus, Vanessa; Chichester, Jessica A; Ebensen, Thomas ( 0000-0001-8906-063X ) ; Schwarz, Katharina; Hartman, Caitlin E; Shoji, Yoko; Guzmán, Carlos A; Yusibov, Vidadi; Sewald, Katherina; Braun, Armin
Abstract:
Annually influenza virus infections are responsible for hospitalization and mortality, especially in high risk groups. Constant antigenic changes in seasonal influenza viruses resulted from antigenic shifts and antigenic drifts, enable emerging of novel virus subtypes that may reduce current vaccine efficacy and impose the continuous revision of vaccine component. Currently available vaccines are usually limited by their production processes in terms of rapid adaptation to new circulating subtypes in high quantities meeting the global demand. Thus, new approaches to rapidly manufacture high yields of influenza vaccines are required. New technologies to reach maximal protection with minimal vaccine doses also need to be developed. In this study, we evaluated the systemic and local immunogenicity of a new double-adjuvanted influenza vaccine administered at the site of infection, the respiratory tract. This vaccine combines a plant-produced H1N1 influenza hemagglutinin antigen (HAC1), a silica nanoparticle-based (SiO₂) drug delivery system and the mucosal adjuvant candidate bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP). Mice were vaccinated by intratracheal route with HAC1/SiO₂ or HAC1/c-di-GMP (single-adjuvanted vaccine) or HAC1/SiO₂/c-di-GMP (double-adjuvanted vaccine) and evaluated for target-specific immune responses, such as hemagglutination inhibition and hemagglutinin-specific IgG titers, as well as local antibody (IgG and IgA) titers in the bronchoalveolar lavage (BAL). Furthermore, the HAC1-specific T-cell re-stimulation potential was assessed using precision-cut lung slices (PCLS) of vaccinated mice. The double-adjuvanted vaccine induced high systemic antibody responses comparable to the systemic vaccination control. In addition, it induced local IgG and IgA responses in the BAL. Furthermore, HAC1 induced a local T-cell response demonstrated by elevated IL-2 and IFN-γ levels in PCLS of c-di-GMP-vaccinated mice upon re-stimulation. Overall, the present study showed the potential of the double-adjuvanted vaccine to induce systemic humoral immune responses in intratracheally vaccinated mice. Furthermore, it induced a strong mucosal immune response, with evidence of antigen-primed T-cells in the lung.
Citation:
A new adjuvanted nanoparticle-based H1N1 influenza vaccine induced antigen-specific local mucosal and systemic immune responses after administration into the lung. 2014, 32 (26):3216-22 Vaccine
Journal:
Vaccine
Issue Date:
30-May-2014
URI:
http://hdl.handle.net/10033/322187
DOI:
10.1016/j.vaccine.2014.04.011
PubMed ID:
24731807
Type:
Article
Language:
en
ISSN:
1873-2518
Appears in Collections:
publications of the research group vaccinology and applied microbiology (VAC)

Full metadata record

DC FieldValue Language
dc.contributor.authorNeuhaus, Vanessaen
dc.contributor.authorChichester, Jessica Aen
dc.contributor.authorEbensen, Thomasen
dc.contributor.authorSchwarz, Katharinaen
dc.contributor.authorHartman, Caitlin Een
dc.contributor.authorShoji, Yokoen
dc.contributor.authorGuzmán, Carlos Aen
dc.contributor.authorYusibov, Vidadien
dc.contributor.authorSewald, Katherinaen
dc.contributor.authorBraun, Arminen
dc.date.accessioned2014-06-23T14:23:39Zen
dc.date.available2014-06-23T14:23:39Zen
dc.date.issued2014-05-30en
dc.identifier.citationA new adjuvanted nanoparticle-based H1N1 influenza vaccine induced antigen-specific local mucosal and systemic immune responses after administration into the lung. 2014, 32 (26):3216-22 Vaccineen
dc.identifier.issn1873-2518en
dc.identifier.pmid24731807en
dc.identifier.doi10.1016/j.vaccine.2014.04.011en
dc.identifier.urihttp://hdl.handle.net/10033/322187en
dc.description.abstractAnnually influenza virus infections are responsible for hospitalization and mortality, especially in high risk groups. Constant antigenic changes in seasonal influenza viruses resulted from antigenic shifts and antigenic drifts, enable emerging of novel virus subtypes that may reduce current vaccine efficacy and impose the continuous revision of vaccine component. Currently available vaccines are usually limited by their production processes in terms of rapid adaptation to new circulating subtypes in high quantities meeting the global demand. Thus, new approaches to rapidly manufacture high yields of influenza vaccines are required. New technologies to reach maximal protection with minimal vaccine doses also need to be developed. In this study, we evaluated the systemic and local immunogenicity of a new double-adjuvanted influenza vaccine administered at the site of infection, the respiratory tract. This vaccine combines a plant-produced H1N1 influenza hemagglutinin antigen (HAC1), a silica nanoparticle-based (SiO₂) drug delivery system and the mucosal adjuvant candidate bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP). Mice were vaccinated by intratracheal route with HAC1/SiO₂ or HAC1/c-di-GMP (single-adjuvanted vaccine) or HAC1/SiO₂/c-di-GMP (double-adjuvanted vaccine) and evaluated for target-specific immune responses, such as hemagglutination inhibition and hemagglutinin-specific IgG titers, as well as local antibody (IgG and IgA) titers in the bronchoalveolar lavage (BAL). Furthermore, the HAC1-specific T-cell re-stimulation potential was assessed using precision-cut lung slices (PCLS) of vaccinated mice. The double-adjuvanted vaccine induced high systemic antibody responses comparable to the systemic vaccination control. In addition, it induced local IgG and IgA responses in the BAL. Furthermore, HAC1 induced a local T-cell response demonstrated by elevated IL-2 and IFN-γ levels in PCLS of c-di-GMP-vaccinated mice upon re-stimulation. Overall, the present study showed the potential of the double-adjuvanted vaccine to induce systemic humoral immune responses in intratracheally vaccinated mice. Furthermore, it induced a strong mucosal immune response, with evidence of antigen-primed T-cells in the lung.en
dc.language.isoenen
dc.rightsArchived with thanks to Vaccineen
dc.titleA new adjuvanted nanoparticle-based H1N1 influenza vaccine induced antigen-specific local mucosal and systemic immune responses after administration into the lung.en
dc.typeArticleen
dc.identifier.journalVaccineen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.