title: α-Galactosylceramide potently augments M2e-induced protective immunity against highly pathogenic H5N1 avian influenza virus infection in mice.
abstract: A new form of influenza A vaccine that can provide broadly cross-protective immunity is central in developing strategies to prepare for the next global flu pandemic. The ectodomain of the M2 protein (M2e) is an attractive target for developing such a kind of vaccine and several approaches have been proposed to overcome its poor immunogenicity nature. Here, we show change to the poor immunogenic characteristic of this antigen. This study demonstrates that α-galactosylceramide, which is an immunomodulatory glycolipid, can greatly enhance the protective immunity induced by M2e peptide absorbed in alum adjuvant. Mice were fully protected against highly pathogenic H5N1 avian influenza virus infection, exhibiting significantly reduced morbidity and lung viral titer after supplementing with α-galactosylceramide. α-Galactosylceramide simultaneously augmented the IgG1 and IgG2a antibody responses. In addition, mice immune sera showed enhanced abilities in binding to native M2 proteins on virus infected cells. The adjuvant also modulated the cytokine release of mice upon infection, upregulated the expressions of IFN-γ, IL-4 and several proinflammatory cytokines. In conclusion, we believe that M2e-peptide supplemented with α-galactosylceramide in alum adjuvant would be a promising vaccine formulation to combat the next influenza pandemic.
authors.affiliation: National Research Center For Wildlife Borne Diseases, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: Chengmin
authors.initials: C
authors.lastname: Wang
authors.forename: Hongxuan
authors.initials: H
authors.lastname: He
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage*; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D005699:Galactosylceramides; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C509609:M2e-HBc influenza vaccine; C493154:alpha-galactosylceramide; D015847:Interleukin-4; C041524:aluminum sulfate; D007371:Interferon-gamma