| 1. |
- De Filette, Marina, et al.
(författare)
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Improved design and intranasal delivery of an M2e-based human influenza A vaccine.
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 24:44-46, s. 6597-601
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Tidskriftsartikel (refereegranskat)abstract
- M2 is the third integral membrane protein of influenza A. M2e, the extracellular, 23 amino acid residues of M2, has been remarkably conserved in all human influenza A strains. This prompted us to evaluate the use of M2e as a potential broad-spectrum immunogen in a mouse model for influenza infection. Genetic fusion of the M2e and hepatitis B virus core (HBc) coding sequences allowed us to obtain highly immunogenic virus-like particles. This M2e-HBc vaccine induced complete protection in mice against a lethal influenza challenge. Protective immunity was obtained regardless of the position of M2e in the M2e-HBc chimera at the amino-terminus or inserted in the immuno-dominant loop of the HBc protein. Increasing the copy number of M2e inserted at the N-terminus from one to three per monomer (240-720 per particle) significantly enhanced the immune response and reduced the number of vaccinations required for complete protection against a lethal challenge with influenza A virus. A series of M2e-HBc constructs was subsequently combined with CTA1-DD, a recombinant cholera toxin A1 derived mucosal adjuvant, to test its efficacy as an intranasally delivered vaccine. All hybrid VLPs tested with CTA1-DD completely protected mice from a potentially lethal infection and, in addition, significantly reduced morbidity. Overall, increased resistance to influenza challenge in the mice correlated with an enhanced Th1-type M2e-specific antibody response induced by vaccination. These results show that M2e is a valid and versatile vaccine candidate to protect against any strain of human influenza A.
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| 2. |
- De Filette, Marina, et al.
(författare)
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The universal influenza vaccine M2e-HBc administered intranasally in combination with the adjuvant CTA1-DD provides complete protection.
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 24:5, s. 544-51
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal vaccination requires effective and safe adjuvants. We have evaluated the non-toxic adjuvant CTA1-DD for mucosal vaccination against influenza. CTA1-DD contains the enzymatically active CTA1 subunit of cholera toxin (CT) genetically fused to a gene encoding a dimer of the D-fragment from Staphylococcus aureus protein A. CTA1-DD only binds to Ig-receptor carrying cells of the immune system. Nasal administration of the universal influenza vaccine M2e-HBc in combination with CTA1-DD completely protected mice from a potentially lethal infection and significantly reduced morbidity. Sera of mice immunized with M2e-HBc + CTA1-DD revealed IgG subclass profiles consistent with an enhanced Th1-type immunity. When the vaccine was administered intraperitoneally, the adjuvant improved the M2e antibody titer in circulation, but did not significantly reduce the morbidity.
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| 3. |
- Grdic Eliasson, Dubravka, et al.
(författare)
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A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.
- 2011
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 29:23, s. 3951-61
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Tidskriftsartikel (refereegranskat)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.
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| 4. |
- Grdic Eliasson, Dubravka, et al.
(författare)
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CTA1-M2e-DD: a novel mucosal adjuvant targeted influenza vaccine.
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 26:9, s. 1243-52
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Tidskriftsartikel (refereegranskat)abstract
- At present few vaccine candidates exists against potentially pandemic influenza virus infections. We provide compelling evidence that a targeted fusion protein based on the CTA1-DD adjuvant and containing tandem repeats of the matrix protein 2 (M2e) ectodomain epitope, CTA1-3M2e-DD, confers strong protective immunity against a potentially lethal challenge infection with influenza virus in mice. The formulation was highly effective for mucosal immunizations and promoted high M2e-specific serum IgG and mucosal IgA antibody titers and an hitherto unknown anti-M2e CD4 T cell immunity. This novel CTA1-3M2e-DD fusion protein combines adjuvant and a conserved influenza A antigen in a promising candidate for a universal anti-influenza vaccine.
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