title: Evaluation of monovalent and bivalent vaccines against lethal Enterovirus 71 and Coxsackievirus A16 infection in newborn mice.
abstract: Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) have caused severe epidemics of hand, foot and mouth disease (HFMD) in the Asia Pacific in recent years, particularly in infants and young children. This disease has become a serious public health problem, as no vaccines or antiviral drugs have been approved for EV71 and CA16 infections. In this study, we compared four monovalent vaccines, including formalin-inactivated EV71 virus (iEV71), EV71 virus-like particles (VLPs) (vEV71), formalin-inactivated CVA16 virus (iCVA16) and CVA16 VLPs (vCVA16), along with two bivalent vaccines, including equivalent doses of formalin-inactivated EV71+CVA16 virus (iEV71+iCVA16) and EV71+CVA16 VLPs (vEV71+vCVA16). The IgG titers and neutralization antibodies titers demonstrated that there are no immune interference exists between the two immunogens of EV71 and CVA16. IgG subclass isotyping revealed that IgG1 and IgG2b were induced primarily in all vaccine groups. Furthermore, cross-neutralization antibodies were elicited in mouse sera against other sub-genotypes of EV71 and CVA16. In vivo challenge experiments showed that the immune sera from vaccinated animals could confer passive protection to newborn mice against lethal challenge with 14 LD50 of EV71 and 50 LD50 of CVA16. Our results indicated that bivalent vaccination is promising for HFMD vaccine development. With the advantage of having a better safety profile than inactivated virus vaccines, VLPs should be used to combine both EV71 and CVA16 antigens as a candidate vaccine for prevention of HFMD virus transmission.
authors.affiliation: a School of Life Sciences ; Jilin University ; Changchun , PR China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Sun
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.forename: Zhenglun
authors.initials: Z
authors.lastname: Liang
authors.forename: Qunying
authors.initials: Q
authors.lastname: Mao
authors.forename: Weiheng
authors.initials: W
authors.lastname: Su
authors.forename: Huafei
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Jin
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhao
authors.forename: Peihu
authors.initials: P
authors.lastname: Fan
authors.forename: Dong
authors.initials: D
authors.lastname: An
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Jingcai
authors.initials: J
authors.lastname: Lu
authors.forename: Xiuping
authors.initials: X
authors.lastname: Lv
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology / Q000517:prevention & control*; D029821:Enterovirus A, Human / Q000276:immunology*; D006232:Hand, Foot and Mouth Disease / Q000276:immunology / Q000517:prevention & control; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology* / Q000627:therapeutic use; D014765:Viral Vaccines / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
keywords: Coxsackievirus A16; Enterovirus 71; HFMD; bivalent vaccines; monovalent vaccine; pseudovirus