title: Validation and evaluation of serological correlates of protection for inactivated enterovirus 71 vaccine in children aged 6-35 months.
abstract: A primary goal of this study was to establish the serological mechanistic correlate of protection (mCoP) for an inactivated Enterovirus 71 (EV71) vaccine.
  
  
  
  We used the Prentice criterion framework and scaled logit model to explore the relationship between the neutralizing antibody (NTAb) and EV71-associated disease, and to build a protection curve for estimating the efficacy of EV71 vaccine. Data of NTAb at day 56 post-vaccination and the occurrence of EV71-associated disease during a 12-month follow-up period were collected from a phase 3 efficacy trial of EV71 vaccine in this study.
  
  
  
  NTAb at day 56 post-vaccination in participants met the Prentice criterion framework. According to the protection curve, the antibody levels of 14.7, 27.8, 55.7, 129.0 and 459.4 (U/mL) were associated with 50%, 60%, 70%, 80% and 90% clinical protection rate, respectively. Vaccine efficacy predicted by the model was 81.5%, which was very similar to the actual vaccine efficacy of 80.4% (95% CI, 58.2, 90.8) observed in the phase 3 trial.
  
  
  
  NTAb titers post-vaccination can be validated as mCoP for evaluating the efficacy of an inactivated enterovirus 71 vaccine, with a titers of 14.7 (U/ml) as a surrogate associated with the protection of 50% against EV71-associated disease.
authors.affiliation: a Department of Epidemiology and Biostatistics , School of Public Health, Nanjing Medical University , Nanjing , China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Jin
authors.affiliation: b Jiangsu Province Center for Disease Control and Prevention , Nanjing , China.|c College of Pharmacy, Third Military Medical University & National Engineering Research Center for Immunological Products , Chongqing , China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Li
authors.affiliation: b Jiangsu Province Center for Disease Control and Prevention , Nanjing , China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: b Jiangsu Province Center for Disease Control and Prevention , Nanjing , China.
authors.forename: Fangyue
authors.initials: F
authors.lastname: Meng
authors.affiliation: d School of Public Health, Southeast University , Nanjing , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: a Department of Epidemiology and Biostatistics , School of Public Health, Nanjing Medical University , Nanjing , China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Yao
authors.affiliation: d School of Public Health, Southeast University , Nanjing , China.
authors.forename: Zhengkai
authors.initials: Z
authors.lastname: Gan
authors.affiliation: a Department of Epidemiology and Biostatistics , School of Public Health, Nanjing Medical University , Nanjing , China.|b Jiangsu Province Center for Disease Control and Prevention , Nanjing , China.
authors.forename: Fengcai
authors.initials: F
authors.lastname: Zhu
mesh_terms: D019138:Antibodies, Blocking; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D002675:Child, Preschool; D004311:Double-Blind Method; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D015164:Vaccines, Inactivated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
keywords: Enterovirus 71 vaccine, Prentice criterion; correlate of protection; surrogate endpoints; the scaled logit model; vaccine efficacy trial