Evaluation of the sublingual route for administration of influenza H5N1 virosomes in combination with the bacterial second messenger c-di-GMP.

2.50
Hdl Handle:
http://hdl.handle.net/10033/235831
Title:
Evaluation of the sublingual route for administration of influenza H5N1 virosomes in combination with the bacterial second messenger c-di-GMP.
Authors:
Pedersen, Gabriel Kristian; Ebensen, Thomas; Gjeraker, Ingrid Hjetland; Svindland, Signe; Bredholt, Geir; Guzmán, Carlos Alberto; Cox, Rebecca Jane
Abstract:
Avian influenza A H5N1 is a virus with pandemic potential. Mucosal vaccines are attractive as they have the potential to block viruses at the site of entry, thereby preventing both disease and further transmission. The intranasal route is safe for the administration of seasonal live-attenuated influenza vaccines, but may be less suitable for administration of pandemic vaccines. Research into novel mucosal routes is therefore needed. In this study, a murine model was used to compare sublingual administration with intranasal and intramuscular administration of influenza H5N1 virosomes (2 µg haemagglutinin; HA) in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di-GMP). We found that sublingual immunisation effectively induced local and systemic H5N1-specific humoral and cellular immune responses but that the magnitude of response was lower than after intranasal administration. However, both the mucosal routes were superior to intramuscular immunisation for induction of local humoral and systemic cellular immune responses including high frequencies of splenic H5N1-specific multifunctional (IL-2+TNF-α+) CD4+ T cells. The c-di-GMP adjuvanted vaccine elicited systemic haemagglutination inhibition (HI) antibody responses (geometric mean titres ≥ 40) both when administered sublingually, intranasally and inramuscularly. In addition, salivary HI antibodies were elicited by mucosal, but not intramuscular vaccination. We conclude that the sublingual route is an attractive alternative for administration of pandemic influenza vaccines.
Affiliation:
The Gade Institute, University of Bergen, Norway. gabriel.pedersen@gades.uib.no
Citation:
Evaluation of the sublingual route for administration of influenza H5N1 virosomes in combination with the bacterial second messenger c-di-GMP. 2011, 6 (11):e26973 PLoS ONE
Journal:
PloS one
Issue Date:
2011
URI:
http://hdl.handle.net/10033/235831
DOI:
10.1371/journal.pone.0026973
PubMed ID:
22069479
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Publications of Dept. Vaccinology (VAC)

Full metadata record

DC FieldValue Language
dc.contributor.authorPedersen, Gabriel Kristianen_GB
dc.contributor.authorEbensen, Thomasen_GB
dc.contributor.authorGjeraker, Ingrid Hjetlanden_GB
dc.contributor.authorSvindland, Signeen_GB
dc.contributor.authorBredholt, Geiren_GB
dc.contributor.authorGuzmán, Carlos Albertoen_GB
dc.contributor.authorCox, Rebecca Janeen_GB
dc.date.accessioned2012-07-26T08:18:45Z-
dc.date.available2012-07-26T08:18:45Z-
dc.date.issued2011-
dc.identifier.citationEvaluation of the sublingual route for administration of influenza H5N1 virosomes in combination with the bacterial second messenger c-di-GMP. 2011, 6 (11):e26973 PLoS ONEen_GB
dc.identifier.issn1932-6203-
dc.identifier.pmid22069479-
dc.identifier.doi10.1371/journal.pone.0026973-
dc.identifier.urihttp://hdl.handle.net/10033/235831-
dc.description.abstractAvian influenza A H5N1 is a virus with pandemic potential. Mucosal vaccines are attractive as they have the potential to block viruses at the site of entry, thereby preventing both disease and further transmission. The intranasal route is safe for the administration of seasonal live-attenuated influenza vaccines, but may be less suitable for administration of pandemic vaccines. Research into novel mucosal routes is therefore needed. In this study, a murine model was used to compare sublingual administration with intranasal and intramuscular administration of influenza H5N1 virosomes (2 µg haemagglutinin; HA) in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di-GMP). We found that sublingual immunisation effectively induced local and systemic H5N1-specific humoral and cellular immune responses but that the magnitude of response was lower than after intranasal administration. However, both the mucosal routes were superior to intramuscular immunisation for induction of local humoral and systemic cellular immune responses including high frequencies of splenic H5N1-specific multifunctional (IL-2+TNF-α+) CD4+ T cells. The c-di-GMP adjuvanted vaccine elicited systemic haemagglutination inhibition (HI) antibody responses (geometric mean titres ≥ 40) both when administered sublingually, intranasally and inramuscularly. In addition, salivary HI antibodies were elicited by mucosal, but not intramuscular vaccination. We conclude that the sublingual route is an attractive alternative for administration of pandemic influenza vaccines.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen_GB
dc.subject.meshAdjuvants, Immunologicen_GB
dc.subject.meshAdministration, Intranasalen_GB
dc.subject.meshAdministration, Mucosalen_GB
dc.subject.meshAdministration, Sublingualen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAntibodies, Viralen_GB
dc.subject.meshAntibody Formationen_GB
dc.subject.meshCell Proliferationen_GB
dc.subject.meshCyclic GMPen_GB
dc.subject.meshDrug Therapy, Combinationen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHemagglutination Inhibition Testsen_GB
dc.subject.meshInfluenza A Virus, H5N1 Subtypeen_GB
dc.subject.meshInfluenza Vaccinesen_GB
dc.subject.meshInterleukin-2en_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred BALB Cen_GB
dc.subject.meshOrthomyxoviridae Infectionsen_GB
dc.subject.meshSalivaen_GB
dc.subject.meshSecond Messenger Systemsen_GB
dc.subject.meshTumor Necrosis Factor-alphaen_GB
dc.subject.meshVaccinationen_GB
dc.subject.meshVirosomesen_GB
dc.titleEvaluation of the sublingual route for administration of influenza H5N1 virosomes in combination with the bacterial second messenger c-di-GMP.en
dc.typeArticleen
dc.contributor.departmentThe Gade Institute, University of Bergen, Norway. gabriel.pedersen@gades.uib.noen_GB
dc.identifier.journalPloS oneen_GB

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