A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus

Dubravka Grdic Eliasson; Anja Helgeby; Karin Schön; Caroline Nygren; Karim El-Bakkouri; Walter Fiers; Xavier Saelens; Karin Bengtsson Lövgren; Ida Nyström; Nils Y Lycke

doi:10.1016/j.vaccine.2011.03.090

A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus

Vaccine. 2011 May 23;29(23):3951-61. doi: 10.1016/j.vaccine.2011.03.090. Epub 2011 Apr 8.

Authors

Dubravka Grdic Eliasson¹, Anja Helgeby, Karin Schön, Caroline Nygren, Karim El-Bakkouri, Walter Fiers, Xavier Saelens, Karin Bengtsson Lövgren, Ida Nyström, Nils Y Lycke

Affiliation

¹ MIVAC - Mucosal Immunobiology & Vaccine Center, Department of Microbiology and Immunology, Institute of Biomedicine, University of Göteborg, 413 90 Göteborg, Sweden.

PMID: 21481325
DOI: 10.1016/j.vaccine.2011.03.090

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic*
Animals
Cholera Toxin / administration & dosage
Cholera Toxin / genetics
Cholera Toxin / immunology*
Genetic Vectors / administration & dosage
Genetic Vectors / immunology*
Humans
ISCOMs* / administration & dosage
ISCOMs* / genetics
ISCOMs* / immunology
Immunity, Mucosal
Immunization
Influenza A Virus, H1N1 Subtype / immunology
Influenza A Virus, H1N1 Subtype / pathogenicity
Influenza A Virus, H3N2 Subtype / immunology
Influenza A Virus, H3N2 Subtype / pathogenicity
Influenza Vaccines* / administration & dosage
Influenza Vaccines* / genetics
Influenza Vaccines* / immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Mucous Membrane / immunology*
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / prevention & control
Orthomyxoviridae Infections / virology
Reassortant Viruses / immunology
Reassortant Viruses / pathogenicity
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology*
Treatment Outcome
Viral Matrix Proteins / administration & dosage
Viral Matrix Proteins / genetics
Viral Matrix Proteins / immunology*

Substances

Adjuvants, Immunologic
CTA1-DD protein, recombinant
ISCOMs
Influenza Vaccines
M2 protein, Influenza A virus
Recombinant Fusion Proteins
Viral Matrix Proteins
Cholera Toxin