title: A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.
abstract: Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4°C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation.
authors.affiliation: MIVAC - Mucosal Immunobiology & Vaccine Center, Department of Microbiology and Immunology, Institute of Biomedicine, University of Göteborg, 413 90 Göteborg, Sweden.
authors.forename: Dubravka Grdic
authors.initials: DG
authors.lastname: Eliasson
authors.forename: Anja
authors.initials: A
authors.lastname: Helgeby
authors.forename: Karin
authors.initials: K
authors.lastname: Schön
authors.forename: Caroline
authors.initials: C
authors.lastname: Nygren
authors.forename: Karim
authors.initials: K
authors.lastname: El-Bakkouri
authors.forename: Walter
authors.initials: W
authors.lastname: Fiers
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
authors.forename: Karin Bengtsson
authors.initials: KB
authors.lastname: Lövgren
authors.forename: Ida
authors.initials: I
authors.lastname: Nyström
authors.forename: Nils Y
authors.initials: NY
authors.lastname: Lycke
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D002772:Cholera Toxin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D016882:ISCOMs / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D016865:Reassortant Viruses / Q000276:immunology / Q000472:pathogenicity; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D002772:Cholera Toxin; D016882:ISCOMs; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C440610:CTA1-DD protein, recombinant; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins