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Improved design and intranasal delivery of an M2e-based human influenza A vaccine.

Journal article
Authors Marina De Filette
Walter Fiers
Wouter Martens
Ashley Birkett
Anna Ramne
Björn Löwenadler
Nils Y Lycke
Willy Min Jou
Xavier Saelens
Published in Vaccine
Volume 24
Issue 44-46
Pages 6597-601
ISSN 0264-410X
Publication year 2006
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 6597-601
Language en
Links dx.doi.org/10.1016/j.vaccine.2006.0...
Keywords Adjuvants, Immunologic, pharmacology, Administration, Intranasal, Animals, Cholera Toxin, pharmacology, Humans, Immunization, Influenza Vaccines, administration & dosage, adverse effects, immunology, Influenza, Human, immunology, prevention & control, Mice, Recombinant Fusion Proteins, immunology, pharmacology, Viral Matrix Proteins, genetics, immunology
Subject categories Medical and Health Sciences

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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