title: Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody against subgenotypes B1, B4, B5 and C4A in adult volunteers.
abstract: BACKGROUND
  Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac) at 5- and 10-µg doses. In this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotypes of EV71 and CVA16.
  
  
  METHODS
  Sixty eligible healthy adults were recruited and vaccinated. Blood samples were obtained on day 0, 21 and 42 and tested against B1, B4, B5, C2, C4A, C4B and CVA16 for cross-neutralizing antibody responses.
  
  
  RESULTS
  The immunogenicity of both 5- and 10- µg doses were found to be very similar. Approximately 45% of the participants had <8 pre-vaccination neutralization titers (Nt) against the B4 vaccine strain. After the first EV71vac immunization, 95% of vaccinees have >4-fold increase in Nt, but there was no further increase in Nt after the second dose. EV71vac induced very strong cross-neutralizing antibody responses in >85% of volunteers without pre-existing Nt against subgenotype B1, B5 and C4A. EV71vac elicited weak cross-neutralizing antibody responses (∼20% of participants) against a C4B and Coxsackie virus A16. Over 90% of vaccinated volunteers did not develop cross-neutralizing antibody responses (Nt<8) against a C2 strain. EV71vac can boost and significantly enhance the neutralizing antibody responses in volunteers who already had pre-vaccination antibodies against EV71 and/or CVA16.
  
  
  CONCLUSIONS
  EV71vac is efficient in eliciting cross-neutralizing antibody responses against EV71 subgenotypes B1, B4, B5, and C4A, and provides the rationale for its evaluation in phase II clinical trials.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01268787.
authors.affiliation: Vaccine Research & Development Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Ai-Hsiang
authors.initials: AH
authors.lastname: Chou
authors.forename: Chia-Chyi
authors.initials: CC
authors.lastname: Liu
authors.forename: Jui-Yuan
authors.initials: JY
authors.lastname: Chang
authors.forename: Renee
authors.initials: R
authors.lastname: Jiang
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Amanda
authors.initials: A
authors.lastname: Tsao
authors.forename: Chien-Long
authors.initials: CL
authors.lastname: Wu
authors.forename: Ju-Lan
authors.initials: JL
authors.lastname: Huang
authors.forename: Chang-Phone
authors.initials: CP
authors.lastname: Fung
authors.forename: Szu-Min
authors.initials: SM
authors.lastname: Hsieh
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Wang
authors.forename: Jen-Ren
authors.initials: JR
authors.lastname: Wang
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Hu
authors.forename: Jen-Ron
authors.initials: JR
authors.lastname: Chiang
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Pele Choi-Sing
authors.initials: PC
authors.lastname: Chong
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D002460:Cell Line; D002522:Chlorocebus aethiops; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000472:pathogenicity; D004769:Enterovirus Infections / Q000188:drug therapy* / Q000276:immunology; D005557:Formaldehyde / Q000494:pharmacology*; D006801:Humans; D015164:Vaccines, Inactivated / Q000627:therapeutic use*; D014709:Vero Cells
chemical_list: D057134:Antibodies, Neutralizing; D015164:Vaccines, Inactivated; D005557:Formaldehyde