Oral Presentation 9th Australasian Virology Society Meeting 2017

A new replication-defective, vaccinia-derived, CHO-manufactured, vaccine vector system (SCV) is effective in preclinical studies. (#30)

Natalie A Prow 1 2 3 , Liang Liu 3 , Eri Nakayama 4 , Tamara H Cooper 3 , Kexin Yan 1 , Preethi Eldi 3 , Jessamine E Hazlewood 1 , Bing Tang 1 , Thuy Le 1 , Yin Xiang X Setoh 5 , Alexander A Khromykh 2 5 , Jody Hobson-Peters 5 , Kerrilyn R Diener 6 , Paul M Howley 7 , John D Hayball 3 6 , Andreas Suhrbier 1 2
  1. Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  2. Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia
  3. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia
  4. Department of Virology I, National Institute of Infectious Diseases, Toyko, Japan
  5. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  6. Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
  7. Sementis Ltd, Berwick, Victoria, 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 an innovative 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 and the VACV host-range factor CP77, named the ‘SCV cell substrate’ (SCS), 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. SCV proved to be fully attenuated in a range of human-derived cell lines and in immunocompromised mice. A single vaccination of mice with SCV-CHIK was able to induce CHIKV-specific antibody responses that were equivalent to those produced by replication-competent VACV-CHIK, could neutralise CHIKV, and provided protection when challenged with CHIKV preventing viremia and the development of arthralgia. 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. Interestingly, prior infection with chikungunya or vaccinia virus did not affect the ability of the vaccine to induce anti-Zika and/or anti-chikungunya antibody responses. 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.