title: AS04-adjuvanted virus-like particles containing multiple M2 extracellular domains of influenza virus confer improved protection.
abstract: The ectodomain of matrix protein 2 (M2e) of influenza virus is suggested to be a rational target for a universal influenza A vaccine. However, there are some concerns that M2e vaccines might not be highly effective in the general population with diverse genetic backgrounds. Here we examined the immunogenicity and protective efficacy of the baculovirus-derived virus-like particles containing multiple M2e (M2eVLP) with AS04 adjuvant in a C57BL/6 mouse strain (H-2(b)). M2eVLP vaccine induced significant levels of M2e-specific IgG in C57BL/6 mice after vaccination. Furthermore, M2eVLP adjuvanted with AS04 was more effective than M2eVLP alone in conferring protection as well as in inducing recall humoral and T cell responses specific for M2e after lethal influenza virus challenge. A mechanistic study provides evidence that activation of dendritic cells by the toll-like receptor 4 agonist MPL in the AS04 adjuvant was associated with interferon-γ producing CD4 T cell responses. Our results suggest that AS04 adjuvanted M2eVLP vaccines have the potential to improve cross-protection.
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Yu-Na
authors.initials: YN
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Animal and Plant Quarantine Agency, Anyang, Gyeonggi-do, South Korea.
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kim
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Cho
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Ko
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Kwon
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address: skang24@gsu.edu.
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D007371:Interferon-gamma; D008050:Lipid A; D058425:Vaccines, Virus-Like Particle; D014763:Viral Matrix Proteins; C532963:ASO4 mixture; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Adjuvants; C57BL/6; Influenza virus; M2e VLPs