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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.

Original publication

DOI

10.4049/jimmunol.172.9.5598

Type

Journal article

Journal

J Immunol

Publication Date

01/05/2004

Volume

172

Pages

5598 - 5605

Keywords

Animals, Antibodies, Viral, Antibody Specificity, Antibody-Dependent Cell Cytotoxicity, Binding Sites, Antibody, Bronchoalveolar Lavage Fluid, Complement C3, Extracellular Fluid, Female, Hepatitis B virus, Immunoglobulin G, Influenza A virus, Influenza Vaccines, Killer Cells, Natural, Lymphocyte Depletion, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Orthomyxoviridae Infections, Protein Structure, Tertiary, T-Lymphocytes, Vaccines, Combined, Viral Matrix Proteins, Virus Inactivation