Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine

Ede Qin, Huiying Shi, Lin Tang, Cuie Wang, Guohui Chang, Zhifen Ding, Kai Zhao, Jian Wang, Ze Chen, Man Yu, Bingyin Si, Jianyuan Liu, Donglai Wu, Xiaojie Cheng, Baoan Yang, Wenming Peng, Qingwen Meng, Bohua Liu, Weiguo Han, Xunnan YinHongyuan Duan, Dawei Zhan, Long Tian, Shuangli Li, Jinsong Wu, Gang Tan, Yi Li, Yuchuan Li, Yonggang Liu, Hong Liu, Fushuang Lv, Yu Zhang, Xiangang Kong, Baochang Fan, Tao Jiang, Shuli Xu, Xiaomei Wang, Changwen Li, Xiaohong Wu, Yongqiang Deng, Min Zhao, Qingyu Zhu

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 β-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 2 μg/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. Findings: 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. Interpretation: 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.

Original languageEnglish (US)
Pages (from-to)1028-1034
Number of pages7
JournalVaccine
Volume24
Issue number7
DOIs
StatePublished - Feb 13 2006
Externally publishedYes

Fingerprint

Severe Acute Respiratory Syndrome
Vero Cells
Haplorhini
monkeys
Vaccines
immune response
vaccines
cells
neutralizing antibodies
Neutralizing Antibodies
high performance liquid chromatography
antibodies
Antibody-Dependent Enhancement
Macaca fascicularis
Propiolactone
neutralization tests
High Pressure Liquid Chromatography
electron microscopes
ion exchange chromatography
ultrafiltration

Keywords

  • Inactivated vaccine
  • Monkey
  • SARS-CoV
  • Severe acute respiratory syndrome

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Qin, E., Shi, H., Tang, L., Wang, C., Chang, G., Ding, Z., ... Zhu, Q. (2006). Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine. Vaccine, 24(7), 1028-1034. https://doi.org/10.1016/j.vaccine.2005.06.038

Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine. / Qin, Ede; Shi, Huiying; Tang, Lin; Wang, Cuie; Chang, Guohui; Ding, Zhifen; Zhao, Kai; Wang, Jian; Chen, Ze; Yu, Man; Si, Bingyin; Liu, Jianyuan; Wu, Donglai; Cheng, Xiaojie; Yang, Baoan; Peng, Wenming; Meng, Qingwen; Liu, Bohua; Han, Weiguo; Yin, Xunnan; Duan, Hongyuan; Zhan, Dawei; Tian, Long; Li, Shuangli; Wu, Jinsong; Tan, Gang; Li, Yi; Li, Yuchuan; Liu, Yonggang; Liu, Hong; Lv, Fushuang; Zhang, Yu; Kong, Xiangang; Fan, Baochang; Jiang, Tao; Xu, Shuli; Wang, Xiaomei; Li, Changwen; Wu, Xiaohong; Deng, Yongqiang; Zhao, Min; Zhu, Qingyu.

In: Vaccine, Vol. 24, No. 7, 13.02.2006, p. 1028-1034.

Research output: Contribution to journalArticle

Qin, E, Shi, H, Tang, L, Wang, C, Chang, G, Ding, Z, Zhao, K, Wang, J, Chen, Z, Yu, M, Si, B, Liu, J, Wu, D, Cheng, X, Yang, B, Peng, W, Meng, Q, Liu, B, Han, W, Yin, X, Duan, H, Zhan, D, Tian, L, Li, S, Wu, J, Tan, G, Li, Y, Li, Y, Liu, Y, Liu, H, Lv, F, Zhang, Y, Kong, X, Fan, B, Jiang, T, Xu, S, Wang, X, Li, C, Wu, X, Deng, Y, Zhao, M & Zhu, Q 2006, 'Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine', Vaccine, vol. 24, no. 7, pp. 1028-1034. https://doi.org/10.1016/j.vaccine.2005.06.038
Qin, Ede ; Shi, Huiying ; Tang, Lin ; Wang, Cuie ; Chang, Guohui ; Ding, Zhifen ; Zhao, Kai ; Wang, Jian ; Chen, Ze ; Yu, Man ; Si, Bingyin ; Liu, Jianyuan ; Wu, Donglai ; Cheng, Xiaojie ; Yang, Baoan ; Peng, Wenming ; Meng, Qingwen ; Liu, Bohua ; Han, Weiguo ; Yin, Xunnan ; Duan, Hongyuan ; Zhan, Dawei ; Tian, Long ; Li, Shuangli ; Wu, Jinsong ; Tan, Gang ; Li, Yi ; Li, Yuchuan ; Liu, Yonggang ; Liu, Hong ; Lv, Fushuang ; Zhang, Yu ; Kong, Xiangang ; Fan, Baochang ; Jiang, Tao ; Xu, Shuli ; Wang, Xiaomei ; Li, Changwen ; Wu, Xiaohong ; Deng, Yongqiang ; Zhao, Min ; Zhu, Qingyu. / Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine. In: Vaccine. 2006 ; Vol. 24, No. 7. pp. 1028-1034.
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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 β-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 2 μg/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. Findings: 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. Interpretation: 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.",
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T1 - Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine

AU - Qin, Ede

AU - Shi, Huiying

AU - Tang, Lin

AU - Wang, Cuie

AU - Chang, Guohui

AU - Ding, Zhifen

AU - Zhao, Kai

AU - Wang, Jian

AU - Chen, Ze

AU - Yu, Man

AU - Si, Bingyin

AU - Liu, Jianyuan

AU - Wu, Donglai

AU - Cheng, Xiaojie

AU - Yang, Baoan

AU - Peng, Wenming

AU - Meng, Qingwen

AU - Liu, Bohua

AU - Han, Weiguo

AU - Yin, Xunnan

AU - Duan, Hongyuan

AU - Zhan, Dawei

AU - Tian, Long

AU - Li, Shuangli

AU - Wu, Jinsong

AU - Tan, Gang

AU - Li, Yi

AU - Li, Yuchuan

AU - Liu, Yonggang

AU - Liu, Hong

AU - Lv, Fushuang

AU - Zhang, Yu

AU - Kong, Xiangang

AU - Fan, Baochang

AU - Jiang, Tao

AU - Xu, Shuli

AU - Wang, Xiaomei

AU - Li, Changwen

AU - Wu, Xiaohong

AU - Deng, Yongqiang

AU - Zhao, Min

AU - Zhu, Qingyu

PY - 2006/2/13

Y1 - 2006/2/13

N2 - 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 β-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 2 μg/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. Findings: 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. Interpretation: 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.

AB - 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 β-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 2 μg/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. Findings: 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. Interpretation: 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.

KW - Inactivated vaccine

KW - Monkey

KW - SARS-CoV

KW - Severe acute respiratory syndrome

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