title: Comparative analysis of the immunogenicity and protective effects of inactivated EV71 vaccines in mice.
abstract: BACKGROUND
  Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD). Three inactivated EV71 whole-virus vaccines of different strains developed by different manufacturers in mainland China have recently entered clinical trials. Although several studies on these vaccines have been published, a study directly comparing the immunogenicity and protective effects among them has not been carried out, which makes evaluating their relative effectiveness difficult. Thus, properly comparing newly developed vaccines has become a priority, especially in China.
  
  
  RESULTS
  This comparative immunogenicity study was carried out on vaccine strains (both live and inactivated), final container products (FCPs) without adjuvant, and corresponding FCPs containing adjuvant (FCP-As) produced by three manufacturers. These vaccines were evaluated by neutralizing antibody (NAb) responses induced by the same or different dosages at one or multiple time points post-immunization. The protective efficacy of the three vaccines was also determined in one-day-old ICR mice born to immunized female mice. Survival rates were observed in these suckling mice after challenge with 20 LD(50) of EV71/048M3C2. Three FCP-As, in a dose of 200 U, generated nearly 100% NAb positivity rates and similar geometric mean titers (GMTs), especially at 14-21 days post-inoculation. However, the dynamic NAb responses were different among three vaccine strains or three FCPs. The FCP-As at the lowest dose used in clinical trials (162 U) showed good protective effects in suckling mice against lethal challenge (90-100% survival), while the ED(50) of NAb responses and protective effects varied among three FCP-As.
  
  
  CONCLUSIONS
  These studies establish a standard method for measuring the immunogenicity of EV71 vaccines in mice. The data generated from our mouse model study indicated a clear dose-response relationship, which is important for vaccine quality control and assessment, especially for predicting protective efficacy in humans when combined with future clinical trial results.
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Mao
authors.forename: Chenghong
authors.initials: C
authors.lastname: Dong
authors.forename: Xiuling
authors.initials: X
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Zengbing
authors.initials: Z
authors.lastname: Guo
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Li
authors.forename: Miao
authors.initials: M
authors.lastname: Xu
authors.forename: Weidong
authors.initials: W
authors.lastname: Yin
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
authors.forename: Xinliang
authors.initials: X
authors.lastname: Shen
authors.forename: Zhenglun
authors.initials: Z
authors.lastname: Liang
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology / Q000627:therapeutic use*; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D057134:Antibodies, Neutralizing; D015164:Vaccines, Inactivated; D014765:Viral Vaccines