DISC – The Next Generation of African swine fever vaccine

November 9th, 2023

Abstract and poster presented at the Victorian Infection and Immunity Network Young Investigator Symposium, Thursday 9th November 2023.

Fan Jia1*, Stacey Lynch1 and David Williams1

1CSIRO, Australian Centre for Disease Preparedness, Geelong, VIC, Australia

African swine fever (ASF) is a contagious disease of pigs that is currently causing a global pandemic [1, 2]. With a nearly 100% fatality rate, ASF has a drastic impact on pig populations, posing a threat to biodiversity and biosecurity [3]. The causative agent of this devastating disease, ASF virus (ASFV) is a large, enveloped double-stranded DNA virus with a genome length varying between 170 and 190 kilobases. The genome contains between 151 and 167 open reading frames encoding for proteins involved in host infection, viral replication, and host immunity evasion[4] . ASFV has a cell tropism for monocytes and macrophages[5] .

The ASFV is known as one of the most challenging pathogens to produce a safe vaccine against because of its complexity. The most promising ASFV vaccine candidates to date are live-attenuated vaccines (LAV), which have been developed by deletion of genes associated with virulence. There are concerns about the use of ASF LAV because of the potential to revert to a virulent phenotype, post vaccination shedding and poor protection in immunocompromised pigs[6] . Therefore, there is a recognised need for a safe vaccine that can provide effective protection against ASFV for pigs. Defective Infectious Single Cycle (DISC) virus vaccines could be the solution that fulfills both safety and immunogenicity profiles[7] . Infection with DISC virus is limited to just one round within host cells, with no further spread, while it allows expression of an array of the viral proteins that are required for the generation of protective immune responses.

Herein, we proposed to select gene(s) of the ASFV genome for generating deletion mutants using innovative genetic engineering tools. Production of a DISC vaccine will be complemented with a DIVA (Differentiating Vaccinated from Infected Animals) strategy to augment disease diagnosis[8] . Complementary cell lines expressing the missing gene(s) in the DISC candidates will enable a defined and scalable cell substrate for downstream manufacture. This work will advance our knowledge in ASF virology, and in a broader context, form the basis for new capabilities that can be applied to other challenging vaccine targets for human and animal health.

References:

  1. Hyeon, J.Y., et al., Whole genome sequencing and phylogenetic analysis of African swine fever virus detected in a backyard pig in Mongolia, 2019. Front Vet Sci, 2023. 10: p. 1094052.
  2. Dixon, L.K., et al., African Swine Fever Epidemiology and Control. Annu Rev Anim Biosci, 2020. 8: p. 221- 246.
  3. ASF evolution since 2005. 2023; Available from: https://www.woah.org/en/disease/african-swine[1]fever/#ui-id-2.
  4. Rojo, G., et al., Replication of African swine fever virus DNA in infected cells. Virology, 1999. 257(2): p. 524- 36.
  5. Dixon, L.K., et al., African swine fever virus evasion of host defences. Virus Res, 2019. 266: p. 25-33.
  6. Han, N., et al., Summary of the Current Status of African Swine Fever Vaccine Development in China. Vaccines (Basel), 2023. 11(4).
  7. Dudek, T. and D.M. Knipe, Replication-defective viruses as vaccines and vaccine vectors. Virology, 2006. 344(1): p. 230-9.
  8. ERDEM, A.E., DIVA (Differentiating Infected from Vaccinated Animals) Vaccines and Strategies. Etlik Veterinary Microbiology, 2022. 33(1): p. 102-109