Assessment of African swine fever vaccine candidate ASFV-G-∆MGF in a reversion to virulence study

Abstract

African swine fever (ASF) has gained panzootic dimensions and commercial vaccines are still unavailable. Recently, a series of live attenuated vaccines has raised hope for an efficacious and safe vaccine, among them “ASFV-G-∆MGF”. We tested the latter in an in vivo reversion to virulence study in accordance with International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products guidelines. Upon forced animal passaging, a virus variant emerged that was associated with transient fever and an increased replication and shedding. However, all animals were healthy upon completion of the study and reversion to significant virulence was not observed. The genomic changes did not affect the recombination site but involved deletions and reorganizations in the terminal regions of the genome. Thus, our study underscores that in-depth safety characterization is needed for live ASF vaccines. For this particular candidate, additional studies should target long-term effects and transmission characteristics before thorough benefit-risk analysis can be carried out.

Characterization of an African Swine Fever Virus Field Isolate from Vietnam with Deletions in the Left Variable Multigene Family Region

“…These mutations could have contributed to the increased virulence of ASFV-GUS-Vietnam observed in this study. This argument is supported by the findings from a recent reversion to virulence in an in vivo study conducted using the ASFV-G-∆MGF strain that was grown in a proprietary cell line [51]. In that study, the cell line-adapted ASFV-G-∆MGF was serially passaged in pigs five times using a strict procedure looking at the highest titers found in target organs.…”

Recent progress on gene-deleted live-attenuated African swine fever virus vaccines

“…However, it has been reported that the HLJ/18-6GD vaccine candidate reverted to virulence after six back-passages in pigs, but no genetic data was provided to explain how this reversion occurred 55 . The genetic stability of the ASFV-G-ΔMGF vaccine candidate has also been assessed by five back-passages in pigs 56 . Starting from the third passage, inoculated pigs experienced transient fever, with some reaching maximum temperatures of 42 °C on days five and six post-inoculation.…”

Advancement in the development of gene/protein-based vaccines against African swine fever virus

“…This vaccine has been reported to provide excellent protection against the Georgia strain (ASFV-G) in animals after a single intramuscular injection ( O'Donnell et al, 2015 ). The vaccine candidate was passaged five times in domestic pigs according to VICH (International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products) guideline 41, and there was no significant virulence reversion observed ( Deutschmann et al, 2023 ). Attenuated live vaccine candidate HLJ/18-7GD from China had the following seven genes deleted: MGF505-1R, MGF505-2R, MGF505-3R, MGF360-12L, MGF360-13L, MGF360-14L, and EP402R ( Chen et al, 2020 ).…”