Improved design and intranasal delivery of an M2e-based human influenza A vaccine.
Vaccine
; 24(44-46): 6597-601, 2006 Nov 10.
Article
en En
| MEDLINE
| ID: mdl-16814430
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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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
3_ND
/
4_TD
Problema de salud:
2_enfermedades_transmissibles
/
3_cholera
/
4_cholera
Asunto principal:
Administración Intranasal
/
Vacunas contra la Influenza
/
Proteínas de la Matriz Viral
/
Gripe Humana
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Vaccine
Año:
2006
Tipo del documento:
Article
País de afiliación:
Bélgica