title: Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine.
abstract: BACKGROUND
  In 2003, severe acute respiratory syndrome (SARS) resulted in hundreds of infections and deaths globally. We aim to assess immunogenicity and protective efficacy of purified inactivated Vero-cell SARS vaccine in monkeys.
  
  
  METHODS
  The cultures of SARS coronavirus (SARS-CoV) BJ-01 strain infected Vero cells were inactivated with beta-propiolactone. Sequential procedures, including ultrafiltration, gel filtration and ion exchange chromatography, were performed to obtain purified inactivated SARS vaccine. The purified SARS vaccine was analyzed with electron microscope, HPLC and Western blotting. We immunized three groups of cynomolgus macaques fascicularis with adjuvant-containing purified vaccine, purified vaccine and unpurified vaccine, respectively, and a fourth group served as a control. Antibody titers were measured by plaque reduction neutralization test. The vaccinated monkeys were challenged with SARS-CoV BJ-01 strain to observe protective efficacy. Additionally, three groups of rhesus monkeys were immunized with different doses of the purified inactivated SARS vaccine (0.5, 1 and 2mug/time/monkey) on days 0 and 7, and the monkeys were challenged with SARS-CoV GZ-01 strain. We assessed the safety of the SARS vaccine and observed whether the antibody dependent enhancement (ADE) occurred under low levels of neutralizing antibody in rhesus.
  
  
  RESULTS
  The purity of SARS vaccine was 97.6% by HPLC identification and reacted with convalescent sera of SARS patients. The purified SARS vaccine induced high levels of neutralizing antibodies and prevented the replication of SARS-CoV in monkeys. Under low levels of neutralizing antibody, no exacerbation of clinical symptoms was observed when the immunized monkeys were challenged with SARS-CoV. In this preliminary animal trial, no side effects were detected when monkeys were immunized with purified SARS vaccine either at normal or large doses.
  
  
  CONCLUSIONS
  The purified inactivated SARS vaccine could induce high levels of neutralizing antibody, and protect the monkeys from the challenge of SARS-CoV. The SARS vaccine prepared in the study appeared to be safe in monkeys.
authors.affiliation: Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Fengtai District, Beijing, PR China. qinede@sohu.com
authors.forename: Ede
authors.initials: E
authors.lastname: Qin
authors.forename: Huiying
authors.initials: H
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Cuie
authors.initials: C
authors.lastname: Wang
authors.forename: Guohui
authors.initials: G
authors.lastname: Chang
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Ding
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Ze
authors.initials: Z
authors.lastname: Chen
authors.forename: Man
authors.initials: M
authors.lastname: Yu
authors.forename: Bingyin
authors.initials: B
authors.lastname: Si
authors.forename: Jianyuan
authors.initials: J
authors.lastname: Liu
authors.forename: Donglai
authors.initials: D
authors.lastname: Wu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Cheng
authors.forename: Baoan
authors.initials: B
authors.lastname: Yang
authors.forename: Wenming
authors.initials: W
authors.lastname: Peng
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Meng
authors.forename: Bohua
authors.initials: B
authors.lastname: Liu
authors.forename: Weiguo
authors.initials: W
authors.lastname: Han
authors.forename: Xunnan
authors.initials: X
authors.lastname: Yin
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Duan
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhan
authors.forename: Long
authors.initials: L
authors.lastname: Tian
authors.forename: Shuangli
authors.initials: S
authors.lastname: Li
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Tan
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Li
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Fushuang
authors.initials: F
authors.lastname: Lv
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiangang
authors.initials: X
authors.lastname: Kong
authors.forename: Baochang
authors.initials: B
authors.lastname: Fan
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Shuli
authors.initials: S
authors.lastname: Xu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Changwen
authors.initials: C
authors.lastname: Li
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wu
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Deng
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D004306:Dose-Response Relationship, Immunologic; D007114:Immunization; D008252:Macaca fascicularis; D008297:Male; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control; D015164:Vaccines, Inactivated / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines