Virus-like particles containing multiple M2 extracellular domains confer improved cross-protection against various subtypes of influenza virus.
Mol Ther
; 21(2): 485-92, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23247101
ABSTRACT
The extracellular domain of M2 (M2e), a small ion channel membrane protein, is well conserved among different human influenza A virus strains. To improve the protective efficacy of M2e vaccines, we genetically engineered a tandem repeat of M2e epitope sequences (M2e5x) of human, swine, and avian origin influenza A viruses, which was expressed in a membrane-anchored form and incorporated in virus-like particles (VLPs). The M2e5x protein with the transmembrane domain of hemagglutinin (HA) was effectively incorporated into VLPs at a several 100-fold higher level than that on influenza virions. Intramuscular immunization with M2e5x VLP vaccines was highly effective in inducing M2e-specific antibodies reactive to different influenza viruses, mucosal and systemic immune responses, and cross-protection regardless of influenza virus subtypes in the absence of adjuvant. Importantly, immune sera were found to be sufficient for conferring protection in naive mice, which was long-lived and cross-protective. Thus, molecular designing and presenting M2e immunogens on VLPs provide a promising platform for developing universal influenza vaccines without using adjuvants.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Virión
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Inmunoglobulina G
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Vacunas contra la Influenza
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Proteínas de la Matriz Viral
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Subtipo H1N1 del Virus de la Influenza A
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Protección Cruzada
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2013
Tipo del documento:
Article