A new replication-defective, vaccinia-derived, CHO-manufactured, vaccine vector system (SCV) is effective in preclinical studies against Zika and chikungunya viruses
Natalie A. Prow1,2, Liang Liu2, Eri Nakayama3, Tamara H. Cooper2, Kexin Yan1, Preethi Eldi2, Jessamine Hazelwood1, Yin Xiang Setoh4, Alexander A Khromykh4, Jody Hobson-Peters4, Kerrilyn R. Diener5, Paul M. Howley6, John D. Hayball2,5, Andreas Suhrbier1
1 QIMR Berghofer Medical Research Institute, Brisbane, Australia; 2School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia; 3Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan; 4School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia; 5Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, Australia; 6Sementis Ltd., Melbourne, Australia
Platform technologies that can be rapidly adapted to develop and produce vaccines on a commercial scale are needed to counter current and emerging infectious disease threats. An adaptable viral-vector with a Chinese hamster ovary (CHO) cell-based vaccine development and manufacturing process may be one way to best achieve this goal. Herein we describe a vaccinia virus (VACV)-derived vaccine platform termed 'Sementis Copenhagen Vector' (SCV), which has been genetically attenuated by deletion of the essential viral assembly gene, D13L. The SCV can be propagated in rescue CHO cells engineered to express D13, thereby providing a biopharmaceutical industry-standard manufacturing pathway to commercial SCV vaccine production. To illustrate the utility of the SCV vaccine platform technology, a SCV-chikungunya virus (CHIKV) vaccine (SCV-CHIK) and a single-vectored Zika chikungunya vaccine (SCV-ZIKA/CHIK) were developed. A single vaccination of mice with SCV-CHIK was able to induce CHIKV-specific antibody responses that could neutralise CHIKV and provide protection following challenge. Furthermore, a single vectored multi-disease vaccine, SCV-ZIKA/CHIK could induce both CHIKV-specific and ZIKA-specific antibody responses and was effective in reducing both Zika virus viraemia and foetal/placental infection in female mice and Zika virus viraemia, testes infection and pathology in male mice. Further validation of the platform has also been achieved in a Zika non-human primate challenge model following a single shot or prime-boost strategy. In summary, we have produced a novel platform technology that can readily be accommodated in a biopharmaceutical industry-standard manufacturing process. A single vector targeting multiple diseases is an innovative approach to reducing “shot burden” for commonly co-circulating viruses.