title: Hexon-modified recombinant E1-deleted adenoviral vectors as bivalent vaccine carriers for Coxsackievirus A16 and Enterovirus 71.
abstract: Hand, foot and mouth disease (HFMD) is a major public health concern in Asia; more efficient vaccines against HFMD are urgently required. Adenoviral (Ad) capsids have been used widely for the presentation of foreign antigens to induce specific immune responses in the host. Here, we describe a novel bivalent vaccine for HFMD based on the hexon-modified, E1-deleted chimpanzee adenovirus serotype 68 (AdC68). The novel vaccine candidate was generated by incorporating the neutralising epitope of Coxsackievirus A16 (CA16), PEP71, into hypervariable region 1 (HVR1), and a shortened neutralising epitope of Enterovirus 71 (EV71), sSP70, into HVR2 of the AdC68 hexon. In order to enhance the immunogenicity of EV71, VP1 of EV71 was cloned into the E1-region of the AdC68 vectors. The results demonstrated that these two epitopes were well presented on the virion surface and had high affinity towards specific antibodies, and VP1 of EV71 was also significantly expressed. In pre-clinical mouse models, the hexon-modified AdC68 elicited neutralising antibodies against both CA16 and EV71, which conferred protection to suckling mice against a lethal challenge of CA16 and EV71. In summary, this study demonstrates that the hexon-modified AdC68 may represent a promising bivalent vaccine carrier against EV71 and CA16 and an epitope-display platform for other pathogens.
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Chao
authors: C
authors: Zhang
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Yong
authors: Y
authors: Yang
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Yudan
authors: Y
authors: Chi
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Jieyun
authors: J
authors: Yin
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Lijun
authors: L
authors: Yan
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Zhiqiang
authors: Z
authors: Ku
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Qingwei
authors: Q
authors: Liu
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: huangzhong@ips.ac.cn.
authors: Zhong
authors: Z
authors: Huang
authors: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: dmzhou@sibs.ac.cn.
authors: Dongming
authors: D
authors: Zhou
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D001208:Asia; D004195:Disease Models, Animal; D004770:Enterovirus / Q000235:genetics / Q000276:immunology*; D029821:Enterovirus A, Human / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006232:Hand, Foot and Mouth Disease / Q000517:prevention & control*; D006801:Humans; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000954:Antigens, Surface; D000939:Epitopes; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: Adenovirus; Bivalent vaccine; Coxsackievirus A16; Enterovirus 71; Hexon