Oral Presentation 12th Australasian Virology Society Meeting 2024

A Recombinant Alphavirus Platform Based On The Australian Insect-Specific Yada Yada Virus (#21)

Mikaela G Bell 1 , Wilson Nguyen 2 , Jessica J Harrison 1 , Rhys H Parry 1 , Gervais Habarugira 1 , Isabella McMahon 1 , Naphak Modhiran 1 , Daniel Watterson 1 3 , Jana Batovska 4 , Stacey E Lynch 4 , Roy A Hall 1 3 , Daniel J Rawle 2 , Jody Hobson-Peters 1 3
  1. School of Chemistry and Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  2. QIMR Berghofer, Brisbane, QLD, Australia
  3. Australian Infectious Disease Research Centre, Brisbane, QLD, Australia
  4. AgriBio Centre for AgriBioscience, Agriculture Victoria Research, Bundoora, VIC, Australia

Alphaviruses are mosquito-borne viruses that cause a range of diseases in humans and animals, with chikungunya virus (CHIKV) alone causing millions of cases worldwide. In Australia, the average annual incidence for the endemic Ross River virus (RRV) is ~5400 cases, with half from Queensland1. Both alphaviruses can cause chronic, debilitating symptoms such as arthritis and fatigue, and treatment and vaccine options are limited. The closely related insect-specific alphaviruses (ISAs) infect only mosquitoes and cannot replicate in vertebrates. Several were discovered in recent years, including the first Australian ISA; Yada Yada virus (YYV)2. In this project, YYV was utilised to construct recombinant viruses for application as potential vaccine candidates and diagnostic tools. Chimeric alphaviruses with the replication machinery of YYV and expressing the structural protein genes of pathogenic alphaviruses (e.g. YYV/CHIKV and YYV/RRV) were constructed using the circular polymerase extension reaction (CPER) reverse genetics method. These chimeric viruses replicated to high titres in mosquito cell culture and did not infect vertebrate cells, retaining the insect-specific host tropism of the YYV genetic backbone. Antigenic analysis confirmed the chimeric viruses were antigenically identical to wild-type pathogenic viruses, and electron microscopy showed pure virions typical of alphaviruses. YYV/CHIKV administered to mice as a two-dose vaccine successfully protected from viraemia and arthritis when challenged with wild-type CHIKV. YYV chimeras represent a versatile platform for alphavirus research, including potential human and veterinary vaccines and future application to diagnostics assays, whilst able to be safely handled at lower biosecurity levels.

  1. 1: National Notifiable Disease Surveillance System. Australian Department of Health. (https://nindss.health.gov.au/pbi-dashboard/).
  2. 2: Batovska J, Buchmann JP, Holmes EC, Lynch SE. Coding-Complete Genome Sequence of Yada Yada Virus, a Novel Alphavirus Detected in Australian Mosquitoes. Microbiology Resource Announcements 2020;9(2). DOI: 10.1128/mra.01476-19.