Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Can vaccination prevent viral persistence? (#72)

Natalie Prow 1 2 3 , Liang Liu 3 , Eri Nakayama 1 4 , Tamara H Cooper 3 , Kexin Yan 1 , Preethi Eldi 3 , Jessamine Hazelwood 1 , Bing Tang 1 , Thuy Le 1 , Yin Xiang Setoh 5 , Alexander A Khromykh 2 5 , Jody Hobson-Peters 5 , Kerrilyn R Diener 3 , Paul M Howley 6 , John D Hayball 3 , Andreas Suhrbier 1 2
  1. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  2. Australian Infectious Disease Research Centre, Brisbane, QLD, Australia
  3. Experimental Therapeutics Laboratory, School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, Adelaide, South Australia, Australia
  4. Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan
  5. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  6. Sementis Ltd, Berwick, Victoria, Australia

Zika and chikungunya viruses have caused major epidemics and are transmitted by Aedes aegypti and/or Aedes albopictus mosquitoes.  The ‘Sementis Copenhagen Vector’ (SCV) system is a recently developed vaccinia-based, multiplication-defective, vaccine vector technology that allows manufacture in modified CHO cells.  Herein we describe a single vector construct SCV vaccine that encodes the structural polyprotein cassettes of both Zika and chikungunya viruses from different loci.  A single prophylactic vaccination of mice induces neutralizing antibodies to both viruses in wild-type and IFNAR-/- mice and protects against (i) chikungunya virus viremia and arthritis in wild-type mice, (ii) Zika virus viremia and fetal/placental infection in female IFNAR-/- mice and (iii) Zika virus viremia and testes infection and pathology in male IFNAR-/- mice.  To our knowledge this represents the first single vector construct, multi-pathogen vaccine encoding large polyproteins, and offers both simplified manufacturing and formulation, and reduced “shot burden” for these often co-circulating arboviruses.  However, Zika virus is known to persist in male testis. The current work evaluates a therapeutic vaccination approach to reduce viral load in the testis following Zika infection. 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.