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

作者：Eliasson Dubravka Grdic; Helgeby Anja; Schon Karin; Nygren Caroline; El Bakkouri Karim; Fiers Walter; Saelens Xavier; Lovgren Karin Bengtsson; Nystrom Ida; Lycke Nils Y^*

来源：Vaccine, 2011, 29(23): 3951-3961.

DOI：10.1016/j.vaccine.2011.03.090

• Adjuvant
• Mucosal IgA
• Vaccine vector
• Influenza A virus
• Cholera toxin
• M2e
• CTA1-DD

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 degrees 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.

• 出版日期2011-5-23