ABSTRACT
Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that crossreacted with human and avian M2 sequences and produced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A.
Subject(s)
Influenza A Virus, H5N1 Subtype/immunology , Influenza Vaccines/administration & dosage , Ion Channels/immunology , Orthomyxoviridae Infections/prevention & control , Vaccination , Viral Matrix Proteins/immunology , Adenoviridae/metabolism , Amino Acid Sequence , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cross Reactions/immunology , Drug Evaluation, Preclinical , Female , Genes, Viral , Genetic Vectors/administration & dosage , Genetic Vectors/metabolism , Immunization Schedule , Influenza Vaccines/immunology , Injections, Intramuscular , Injections, Intraperitoneal , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Orthomyxoviridae Infections/blood , Recombinant Proteins/biosynthesis , Recombinant Proteins/immunology , Sequence Alignment , T-Lymphocytes/immunology , Vaccines, DNA/immunology , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , Viral Matrix Proteins/genetics , Viral Matrix Proteins/metabolismABSTRACT
We report here a study of T and B cell development and function in mice with disruption of the vasopressin receptor 1a (v1a) gene. Loss of the v1a receptor caused a shift from IgM(high)/IgD(high) to the more mature IgM(low)/IgD(high) B cells, a significantly greater extent of splenic B cells proliferation in response to anti-IgM stimulation, and enhanced IgG1 and IgG2b production in response to immune challenge with T-dependent antigen. B-1 cells were increased in v1a(-/-) mice. In contrast, T cell differentiation and activation were normal in v1a(-/-) mice. Our data identify a novel function for v1a in the periphery as a negative regulator of B cell receptor (BCR) signaling. These data suggest that in addition to its other stress-related effects, vasopressin may also serve as a counter-regulatory restraint upon the immune system during fight or flight situations.
