title: Nanoclusters self-assembled from conformation-stabilized influenza M2e as broadly cross-protective influenza vaccines.
abstract: Influenza vaccines with broad cross-protection are urgently needed. The highly conserved ectodomain of the influenza matrix protein 2 (M2e) can be a promising candidate if its low immunogenicity was overcome. In this study, we generated protein nanoclusters self-assembled from conformation-stabilized M2e tetramers (tM2e) to improve its immunogenicity. The resulting nanoclusters showed an average hydrodynamic diameter of 227 nm. Vaccination with the nanoclusters by an intranasal route elicited high levels of serum antigen-specific IgG in mice (approximately 100-fold higher than that obtained with soluble tM2e), as well as antigen-specific T cell and mucosal antibody responses. The immunity conferred complete protection against lethal challenge with homo- as well as heterosubtypic viruses. These results demonstrate that nanoclusters assembled from conformation-stabilized M2e are promising as a potential universal influenza A vaccine. Self-assembly into nanoclusters represents a novel approach for increasing the immunogenicity of vaccine antigens.
  
  
  BACKGROUND
  In order to develop more effective influenza vaccination, the highly conserved ectodomain of M2e could be a promising candidate. Unfortunately, it is a weak antigen for vaccination purposes. In this study, self-assembled protein nanoclusters of tM2e were generated and tested. The nanoclusters demonstrated superior vaccination properties, with complete protection against lethal challenge in the studied rodent model, raising hope for the introduction of similar vaccines to challenge human influenza outbreaks.
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Georgia Institute of Technology, School of Chemical and Biomolecular Engineering, Atlanta, GA, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Hess
authors.affiliation: Georgia Institute of Technology, School of Chemical and Biomolecular Engineering, Atlanta, GA, USA.
authors.forename: Timothy Z
authors.initials: TZ
authors.lastname: Chang
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Georgia Institute of Technology, School of Chemical and Biomolecular Engineering, Atlanta, GA, USA. Electronic address: julie.champion@chbe.gatech.edu.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Champion
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: rcompan@emory.edu.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: bwang3@emory.edu.
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000941:Antigens / Q000276:immunology; D000956:Antigens, Viral; D018899:CpG Islands; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D053758:Nanoparticles; D036103:Nanotechnology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D010455:Peptides; D011994:Recombinant Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D000941:Antigens; D000956:Antigens, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D010455:Peptides; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Cross protection; Matrix protein 2 (M2); Nanocluster