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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

Adjuvants

Immunologic

Animals

Cholera Toxin

administration & dosage

genetics

immunology

Genetic Vectors

administration & dosage

immunology

Humans

ISCOMs

administration & dosage

genetics

immunology

Immunity

Mucosal

Immunization

Influenza A Virus

H1N1 Subtype

immunology

pathogenicity

Influenza A Virus

H3N2 Subtype

immunology

pathogenicity

Influenza Vaccines

administration & dosage

genetics

immunology

Mice

Mice

Inbred BALB C

Mice

Inbred C57BL

Mice

Transgenic

Mucous Membrane

immunology

Orthomyxoviridae Infections

immunology

prevention & control

virology

Reassortant Viruses

immunology

pathogenicity

Recombinant Fusion Proteins

administration & dosage

genetics

immunology

Treatment Outcome

Viral Matrix Proteins

administration & dosage

genetics

immunology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)