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

• Published in: Molecular therapy Vol. 25; no. 10; pp. 2332 - 2344
• Main Authors: Eldi, Preethi, Cooper, Tamara H., Liu, Liang, Prow, Natalie A., Diener, Kerrilyn R., Howley, Paul M., Suhrbier, Andreas, Hayball, John D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.10.2017; Elsevier Limited; American Society of Gene & Cell Therapy
• Subjects: Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; antibody; Antigens; Arthritis; Cell lines; chikungunya; Chikungunya Fever - immunology; Chikungunya Fever - prevention & control; Chikungunya virus; Chikungunya virus - immunology; CHO Cells; Clonal deletion; Cricetulus; Design; Epidemics; Experiments; Gene deletion; Gene expression; Genomes; Laboratories; live vectored vaccines; Medical research; Multiplication & division; Original; poxvirus; Proteins; R&D; Rabies; Research & development; Scholarships & fellowships; Smallpox; Statistical analysis; Stockholders; vaccine; vaccine platform; Vaccines; vaccinia virus; Vaccinia virus - immunology; Viral Vaccines - immunology; Viremia; Queensland Australia; Australia; Europe; vaccine; antibody; vaccine platform; poxvirus; vaccinia virus; chikungunya; live vectored vaccines
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2017.06.017

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. [Display omitted] Eldi et al. report the development of the Sementis Copenhagen Vector technology, a multiplication-defective poxvirus-derived vaccine platform with a complementing CHO-based cell substrate line designed for large-scale vaccine stock manufacture. The utility of the technology was illustrated by the development of a safe and protective vaccine against chikungunya virus challenge.