title: A combination vaccine comprising of inactivated enterovirus 71 and coxsackievirus A16 elicits balanced protective immunity against both viruses.
abstract: Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which is an infectious disease frequently occurring in children. A bivalent vaccine against both EV71 and CA16 is highly desirable. In the present study, we compare monovalent inactivated EV71, monovalent inactivated CA16, and a combination vaccine candidate comprising of both inactivated EV71 and CA16, for their immunogenicity and in vivo protective efficacy. The two monovalent vaccines were found to elicit serum antibodies that potently neutralized the homologous virus but had no or weak neutralization activity against the heterologous one; in contrast, the bivalent vaccine immunized sera efficiently neutralized both EV71 and CA16. More importantly, passive immunization with the bivalent vaccine protected mice against either EV71 or CA16 lethal infections, whereas the monovalent vaccines only prevented the homologous but not the heterologous challenges. Together, our results demonstrate that the experimental bivalent vaccine comprising of inactivated EV71 and CA16 induces a balanced protective immunity against both EV71 and CA16, and thus provide proof-of-concept for further development of multivalent vaccines for broad protection against HFMD.
authors.affiliation: Center for Vaccine Sciences, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Yicun
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Center for Vaccine Sciences, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ku
authors.affiliation: Center for Vaccine Sciences, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Center for Vaccine Sciences, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Leng
authors.affiliation: Center for Vaccine Sciences, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Electronic address: huangzhong@sibs.ac.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000517:prevention & control*; D004770:Enterovirus; D029821:Enterovirus A, Human; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000517:prevention & control; D007116:Immunization, Passive; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control; D017778:Vaccines, Combined / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D017778:Vaccines, Combined; D014765:Viral Vaccines
keywords: Bivalent vaccine; Coxsackievirus A16; Enterovirus 71; Neutralizing antibody; Passive protection