Production of a Chikungunya Vaccine Using a CHO Cell and Attenuated Viral-Based Platform Technology

被引:18
作者
Eldi, Preethi [1 ,2 ]
Cooper, Tamara H. [1 ,2 ]
Liu, Liang [1 ,2 ]
Prow, Natalie A. [3 ]
Diener, Kerrilyn R. [1 ,2 ,4 ,5 ]
Howley, Paul M. [1 ,2 ,6 ]
Suhrbier, Andreas [3 ]
Hayball, John D. [1 ,2 ,4 ,5 ]
机构
[1] Univ South Australia, Expt Therapeut Lab, Hanson Inst, Adelaide, SA 5000, Australia
[2] Univ South Australia, Sansom Inst Hlth Res, Sch Pharm & Med Sci, Adelaide, SA 5000, Australia
[3] QIMR Berghofer Med Res Inst, Brisbane, Qld 4029, Australia
[4] Univ Adelaide, Robinson Res Inst, Adelaide, SA 5005, Australia
[5] Univ Adelaide, Adelaide Med Sch, Adelaide, SA 5005, Australia
[6] Sementis Ltd, Melbourne, Vic 3000, Australia
基金
澳大利亚研究理事会; 英国医学研究理事会;
关键词
VIRUS; GENE; IMMUNITY; PROTEIN; MVA; REPLICATION; EXPRESSION; RESPONSES; SELECTION; DURATION;
D O I
10.1016/j.ymthe.2017.06.017
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Vaccinia-based systems have been extensively explored for the development of recombinant vaccines. Herein we describe an innovative vaccinia virus (VACV)-derived vaccine platform technology termed Sementis Copenhagen Vector (SCV), which was rendered multiplication-defective by targeted deletion of the essential viral assembly gene D13L. A SCV cell substrate line was developed for SCV vaccine production by engineering CHO cells to express D13 and the VACV host-range factor CP77, because CHO cells are routinely used for manufacture of biologics. To illustrate the utility of the platform technology, a SCV vaccine against chikungunya virus (SCV-CHIK) was developed and shown to be multiplication-defective in a range of human cell lines and in immunocompromised mice. A single vaccination of mice with SCV-CHIK induced antibody responses specific for chikungunya virus (CHIKV) that were similar to those raised following vaccination with a replication-competent VACV-CHIK and able to neutralize CHIKV. Vaccination also provided protection against CHIKV challenge, preventing both viremia and arthritis. Moreover, SCV retained capacity as an effective mouse smallpox vaccine. In summary, SCV represents a new and safe vaccine platform technology that can be manufactured in modified CHO cells, with pre-clinical evaluation illustrating utility for CHIKV vaccine design and construction.
引用
收藏
页码:2332 / 2344
页数:13
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