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

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

2024 | Hiep L. X. Vu & D. Scott McVey
Recent progress on gene-deleted live-attenuated African swine fever virus (ASFV) vaccines has focused on developing safe and effective vaccines by deleting virulence genes from ASFV strains. ASFV is a highly lethal disease in pigs, with mortality rates approaching 100%. Live-attenuated vaccines (LAVs) produced by deleting virulence genes have shown promising safety and efficacy in both experimental and field conditions. Several gene-deleted LAV vaccine candidates have been developed, targeting different virulence genes. The ASFV genome contains 150–190 open reading frames (ORFs) and is divided into four groups of virulence genes: those involved in viral genome replication and transcription, genes from the multigene family (MGF) located at both 5' and 3' termini, genes involved in hemadsorption and putative cellular attachment factors, and novel genes with unknown functions. Deletion of these genes can lead to attenuation and protection against ASFV. Several LAV vaccine candidates have been generated by deleting genes involved in viral genome replication and transcription, such as the thymidine kinase (TK) gene and the RNA helicase superfamily genes. However, these deletions often resulted in over-attenuation or no protection. Deletion of MGF genes, such as six MGF genes (MGF505-1R, MGF360-12L, MGF360-13L, MGF360-14L, MGF505-2R, and MGF505-3R), led to full attenuation and complete protection against a lethal challenge with the parental virus. Deletion of genes involved in hemadsorption, such as EP402R and EP153R, also resulted in attenuated viruses. Deletion of the CD2v gene (EP402R) significantly reduced viral loads in pigs and provided protection against lethal challenge. Deletion of the NL, UK, and 9GL genes also led to attenuated viruses with protective efficacy. Simultaneous deletion of multiple virulence determinants, such as CD2v and DP148R, resulted in fully attenuated viruses with complete protection against lethal challenge. Additionally, the deletion of the I177L gene led to a highly attenuated virus that provided complete protection against a lethal challenge. The development of LAV vaccines has also focused on incorporating a DIVA marker to differentiate between vaccinated and infected animals. Deletion of immunogenic genes, such as E184L and MGF100-5L, has been explored to enhance the DIVA potential of LAV vaccines. Overall, gene-deleted LAV vaccines have shown promising results in terms of safety and efficacy, with several candidates demonstrating complete protection against lethal challenge. However, challenges remain in ensuring the stability and safetyRecent progress on gene-deleted live-attenuated African swine fever virus (ASFV) vaccines has focused on developing safe and effective vaccines by deleting virulence genes from ASFV strains. ASFV is a highly lethal disease in pigs, with mortality rates approaching 100%. Live-attenuated vaccines (LAVs) produced by deleting virulence genes have shown promising safety and efficacy in both experimental and field conditions. Several gene-deleted LAV vaccine candidates have been developed, targeting different virulence genes. The ASFV genome contains 150–190 open reading frames (ORFs) and is divided into four groups of virulence genes: those involved in viral genome replication and transcription, genes from the multigene family (MGF) located at both 5' and 3' termini, genes involved in hemadsorption and putative cellular attachment factors, and novel genes with unknown functions. Deletion of these genes can lead to attenuation and protection against ASFV. Several LAV vaccine candidates have been generated by deleting genes involved in viral genome replication and transcription, such as the thymidine kinase (TK) gene and the RNA helicase superfamily genes. However, these deletions often resulted in over-attenuation or no protection. Deletion of MGF genes, such as six MGF genes (MGF505-1R, MGF360-12L, MGF360-13L, MGF360-14L, MGF505-2R, and MGF505-3R), led to full attenuation and complete protection against a lethal challenge with the parental virus. Deletion of genes involved in hemadsorption, such as EP402R and EP153R, also resulted in attenuated viruses. Deletion of the CD2v gene (EP402R) significantly reduced viral loads in pigs and provided protection against lethal challenge. Deletion of the NL, UK, and 9GL genes also led to attenuated viruses with protective efficacy. Simultaneous deletion of multiple virulence determinants, such as CD2v and DP148R, resulted in fully attenuated viruses with complete protection against lethal challenge. Additionally, the deletion of the I177L gene led to a highly attenuated virus that provided complete protection against a lethal challenge. The development of LAV vaccines has also focused on incorporating a DIVA marker to differentiate between vaccinated and infected animals. Deletion of immunogenic genes, such as E184L and MGF100-5L, has been explored to enhance the DIVA potential of LAV vaccines. Overall, gene-deleted LAV vaccines have shown promising results in terms of safety and efficacy, with several candidates demonstrating complete protection against lethal challenge. However, challenges remain in ensuring the stability and safety
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Understanding Recent progress on gene-deleted live-attenuated African swine fever virus vaccines