title: Characterization of the murine Th2 response to immunization with liposomal M2e influenza vaccine.
abstract: While the current influenza vaccine strategy is dependent on eliciting neutralizing antibodies to the hemagglutinin (H or HA) surface glycoprotein, antigenic drifts and occasional antigenic shifts necessitate constant surveillance and annual updates to the vaccine components. The ectodomain of the matrix 2 (M2e) channel protein has been proposed as a universal vaccine candidate, although it has not yet been shown to elicit neutralizing antibodies. Utilizing a liposome-based vaccine technology, an M2e vaccine (L-M2e-HD/MPL) was tested and shown to stimulate the production of anti-M2e antibodies which precipitated with whole virus and inhibited viral cell lysis by multiple type A strains of influenza virus using a novel in vitro assay. The anti-M2e antibodies also conferred complete protection following passive transfer from L-M2e-HD/MPL vaccinated mice to naïve mice challenged with H1N1 virus. Significantly higher levels of IL-4 compared to IFN-γ were secreted by the splenocytes of L-M2e-HD/MPL vaccinated mice incubated with M2e. In addition, depletion of CD4 cells or CD4 cells plus CD8 cells from L-M2e-HD/MPL vaccinated mice using monoclonal antibodies markedly decreased the level of protection of the vaccine when compared to just CD8 depletion of L-M2e-HD/MPL vaccinated mice. These results suggest that the protective immune response elicited by this vaccine is mediated primarily by a Th2 mechanism.
authors.affiliation: California State Polytechnic University Pomona, 3801 West Temple Ave, Pomona, CA 91768, USA. jpadler@csupomona.edu
authors.forename: Jill
authors.initials: J
authors.lastname: Adler-Moore
authors.forename: Meilen
authors.initials: M
authors.lastname: Munoz
authors.forename: Hana
authors.initials: H
authors.lastname: Kim
authors.forename: Juan
authors.initials: J
authors.lastname: Romero
authors.forename: Terrence
authors.initials: T
authors.lastname: Tumpey
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.forename: Chris
authors.initials: C
authors.lastname: Petro
authors.forename: William
authors.initials: W
authors.lastname: Ernst
authors.forename: Suzie
authors.initials: S
authors.lastname: Kosina
authors.forename: Gretchen
authors.initials: G
authors.lastname: Jimenez
authors.forename: Gary
authors.initials: G
authors.lastname: Fujii
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008050:Lipid A / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology; D008081:Liposomes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018418:Th2 Cells / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D008050:Lipid A; D008081:Liposomes; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C048436:monophosphoryl lipid A