Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity.
Vaccination of mice with a peptide corresponding to the extracellular part of M2 protein coupled to the immunodominant domain of hepatitis B core can protect mice from a lethal challenge with influenza A virus. As the extracellular part of M2 protein is highly conserved in all known human influenza...
| Autors principals: | , , , |
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| Format: | Journal article |
| Idioma: | English |
| Publicat: |
2004
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| _version_ | 1826305996398526464 |
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| author | Jegerlehner, A Schmitz, N Storni, T Bachmann, M |
| author_facet | Jegerlehner, A Schmitz, N Storni, T Bachmann, M |
| author_sort | Jegerlehner, A |
| collection | OXFORD |
| description | Vaccination of mice with a peptide corresponding to the extracellular part of M2 protein coupled to the immunodominant domain of hepatitis B core can protect mice from a lethal challenge with influenza A virus. As the extracellular part of M2 protein is highly conserved in all known human influenza A strains, such a vaccine may protect against all human influenza A strains, which would represent a major advantage over current vaccine strategies. The present study demonstrates that protection is mediated exclusively by Abs, a very important feature of a successful preventive vaccine. However, these Abs neither bind efficiently to the free virus nor neutralize virus infection, but bind to M2 protein expressed on the surface of virus-infected cells. The presence of NK cells is important for protection, whereas complement is not, supposing that protection is mediated via Ab-dependent, cell-mediated cytotoxicity. The absence of neutralizing Abs results in much weaker protection than that achieved by vaccination with UV-inactivated influenza virus. Specifically, whereas neutralizing Abs completely eliminate signs of disease even at high viral challenge doses, M2-specific Abs cannot prevent infection, but merely reduce disease at low challenge doses. M2-specific Abs fail to protect from high challenge doses, as vaccinated mice undergo lethal infection under these conditions. In conclusion, protection mediated by M2-hepatitis B core vaccine would be insufficient during the yearly epidemics, for which full protection is desirable, and overall is clearly inferior to protection achieved by immunization with classical inactivated viral preparations. |
| first_indexed | 2024-03-07T06:41:14Z |
| format | Journal article |
| id | oxford-uuid:f95a38f2-3ba8-44c6-8b05-0800a8152955 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:41:14Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:f95a38f2-3ba8-44c6-8b05-0800a81529552022-03-27T12:57:20ZInfluenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f95a38f2-3ba8-44c6-8b05-0800a8152955EnglishSymplectic Elements at Oxford2004Jegerlehner, ASchmitz, NStorni, TBachmann, MVaccination of mice with a peptide corresponding to the extracellular part of M2 protein coupled to the immunodominant domain of hepatitis B core can protect mice from a lethal challenge with influenza A virus. As the extracellular part of M2 protein is highly conserved in all known human influenza A strains, such a vaccine may protect against all human influenza A strains, which would represent a major advantage over current vaccine strategies. The present study demonstrates that protection is mediated exclusively by Abs, a very important feature of a successful preventive vaccine. However, these Abs neither bind efficiently to the free virus nor neutralize virus infection, but bind to M2 protein expressed on the surface of virus-infected cells. The presence of NK cells is important for protection, whereas complement is not, supposing that protection is mediated via Ab-dependent, cell-mediated cytotoxicity. The absence of neutralizing Abs results in much weaker protection than that achieved by vaccination with UV-inactivated influenza virus. Specifically, whereas neutralizing Abs completely eliminate signs of disease even at high viral challenge doses, M2-specific Abs cannot prevent infection, but merely reduce disease at low challenge doses. M2-specific Abs fail to protect from high challenge doses, as vaccinated mice undergo lethal infection under these conditions. In conclusion, protection mediated by M2-hepatitis B core vaccine would be insufficient during the yearly epidemics, for which full protection is desirable, and overall is clearly inferior to protection achieved by immunization with classical inactivated viral preparations. |
| spellingShingle | Jegerlehner, A Schmitz, N Storni, T Bachmann, M Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. |
| title | Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. |
| title_full | Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. |
| title_fullStr | Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. |
| title_full_unstemmed | Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. |
| title_short | Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. |
| title_sort | influenza a vaccine based on the extracellular domain of m2 weak protection mediated via antibody dependent nk cell activity |
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