title: Enhanced immune response induced by a potential influenza A vaccine based on branched M2e polypeptides linked to tuftsin.
abstract: Vaccination is the most effective means for preventing influenza-associated morbidity and mortality. Since the influenza virus mutates frequently, the virus strains for new vaccine production should be changed according to predicted epidemic strains. The extracellular domain of matrix protein 2 (M2e) is 24 amino acids long, which is highly conserved and therefore a good target for the development of a universal vaccine which may protect against a much wider range of influenza A virus strains. However its low antigenicity and immunogenicity, which are related to its small size, poses a big challenge for vaccine development. Multiple antigen peptide system (MAP) is based on an inert core molecule of radially branching lysine dendrites onto which a number of peptide antigens are anchored. Tuftsin is an immuno-stimulant molecule peptide. Here we developed a novel peptide vaccine by connecting a tuftsin to a branched, four-copy M2e. Not only did this increase the molecular mass, but also potentiate the immunogenicity. Two branched peptides, (M2e)4-tuftsin and (M2e)4-G4(tuftsin was replaced with four glycines), and a M2e monomer were synthesized using standard solid-phase methods. In vitro and in vivo studies were performed to compare their antigenicity and immunogenicity. Experiments in BALB/c mice demonstrated that the branched M2e could induce stronger humoral and cellular immune responses than the M2e monomer, and (M2e)4-tuftsin induced stronger humoral and cellular immune response than (M2e)4-G4. After lethal challenge with influenza virus PR8 strain, up to 80% of the animals in the (M2e)4-tuftsin vaccinated group still survived, in contrast to 44% in the (M2e)4-G4 group and 30% in the M2e monomer group. The combination of branched polypeptides and tuftsin in vaccine design is presented here for the first time, and the results show that the new construct is a promising candidate for a universal vaccine against the influenza A virus.
authors.affiliation: Institute for Viral Disease Control and Prevention, China CDC, Changbai Road 155, Beijing, 102206, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Guo
authors.forename: Su
authors.initials: S
authors.lastname: Han
authors.forename: Lihong
authors.initials: L
authors.lastname: Yao
authors.forename: Aijun
authors.initials: A
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Bo
authors.forename: Pengwei
authors.initials: P
authors.lastname: Xu
authors.forename: Jiyong
authors.initials: J
authors.lastname: Yin
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D016019:Survival Analysis; D014405:Tuftsin / Q000737:chemistry / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007252:Influenza Vaccines; D014405:Tuftsin; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins