African swine fever virus is currently present in all of the world’s continents apart from Antarctica, and efforts to control the disease are hampered by the lack of a commercially available vaccine. The Babraham large white pig is a highly inbred line that could represent a powerful tool to improve our understanding of the protective immune responses to this complex pathogen; however, previous studies indicated differential vaccine responses after the African swine fever virus challenge of inbred minipigs with different swine leukocyte antigen haplotypes. Lymphocyte numbers and African swine fever virus-specific antibody and T-cell responses were measured in inbred and outbred animals after inoculation with a low virulent African swine fever virus isolate and subsequent challenge with a related virulent virus. Surprisingly, diminished immune responses were observed in the Babraham pigs when compared to the outbred animals, and the inbred pigs were not protected after challenge. Recovery of Babraham pigs after challenge weakly correlated with antibody responses, whereas protective responses in outbred animals more closely correlated with the T-cell response. The Babraham pig may, therefore, represent a useful model for studying the role of antibodies in protection against the African swine fever virus.

African swine fever (ASF) is a lethal disease in pigs that has grave socio-economic implications worldwide. For the development of vaccines against the African swine fever virus (ASFV), immunogenic antigens that generate protective immune responses need to be identified. There are over 150 viral proteins—many of which are uncharacterized—and humoral immunity to ASFV has not been closely examined. To profile antigen-specific antibody responses, we developed luciferase-linked antibody capture assays (LACAs) for a panel of ASFV capsid proteins and screened sera from inbred and outbred animals that were previously immunized with low-virulent ASFV before challenge with virulent ASFV. Antibodies to B646L/p72, D117L/p17, M1249L, and E120R/p14.5 were detected in this study; however, we were unable to detect B438L-specific antibodies. Anti-B646L/p72 and B602L antibodies were associated with recovery from disease after challenges with genotype I OUR T88/1 but not genotype II Georgia 2007/1. Antibody responses against M1249L and E120R/p14.5 were observed in animals with reduced clinical signs and viremia. Here, we present LACAs as a tool for the targeted profiling of antigen-specific antibody responses to inform vaccine development.

African swine fever virus (ASFV) causes a lethal hemorrhagic disease in domestic pigs, wild boar, and other members of the genus Sus . Since the introduction of the virus into Georgia in 2007, the disease has spread across Eurasia causing the deaths of millions of animals and the production loss of more than 100 million with a significant socioeconomic impact. Modified live virus vaccines have been licensed and tested in several countries, but there are some residual safety concerns and the efficacy in the field is yet to be established. A subunit vaccine would provide a significant biosafety advantage and avoid the use of live African swine fever virus and would enable deployment of a simple distinguish infected from vaccinated animals (DIVA) strategy. However, the development of effective subunit vaccines has been slow due in part to the complexity of the virus and a poor understanding of the protective immune response. A pool of six viral genes vectored using replication-deficient adenoviruses could protect pigs against genotype I challenge; however, a combination of vectors partially tailored to genotype II ASFV was not successful after a genotype II challenge. Here, we provide immunogenicity and challenge data from a study using genotype II ASFV genes vectored using replication-deficient simian adenoviruses. The six antigens previously shown to protect against severe disease caused by genotype I challenge were supplemented with additional antigens, but these were not sufficient to prevent clinical disease after challenge with genotype II ASFV. IMPORTANCE: African swine fever is a viral hemorrhagic disease of domestic and wild pigs that poses a significant threat to farmers and global food security. Millions of animals have been lost due to the disease itself, control measures, and the knock-on effect on the pig production chain. African swine fever is also a conservation risk as it infects and kills endangered indigenous pigs in southern and eastern Asia and Oceania. Disease control efforts are in part frustrated by the lack of a safe and effective vaccine. Modified live virus vaccines are being deployed in select countries; however, a subunit vaccine like those developed for COVID would alleviate safety concerns with using live viruses in the field. We tested a combination of eight different virus genes delivered using replication-deficient adenoviruses and showed that they induced immune responses in pigs but did not lead to protection against disease.

Effective immune defence and pathogen clearance requires coordination between innate and adaptive immune responses. However, virulent African swine fever virus (ASFV), which has a high case fatality rate in pigs, causes severe disease by exploiting multiple immune evasion strategies to suppress host responses. The global spread of Georgia 2007/1 and its derivatives poses a significant threat to the pig industry and global food security. Although modified live virus vaccines for ASF exist, multiple safety concerns have restricted their use internationally. Conversely, subunit vaccine candidates have not matched the protective efficacy of modified live virus vaccines. This highlights the need to further investigate ASFV-induced immunopathology to support the development of next-generation ASF vaccines. Immune dynamics in whole blood and lymphoid tissues were examined over time after oronasal infection with Georgia 2007/1. CD4+ T cells, γδ-TCR+ T cells and CD21+ B cells were impacted by lymphopenia, and initial immune activation was detected. However, as the disease progressed, impaired maintenance and depletion of adaptive immune cells, such as CD4+ T cells and professional antigen-presenting dendritic cells and macrophages, important mediators at the innate-adaptive immune interface, was observed. This reduction of cells may have compromised the innate-adaptive immune axis, weakening host ability to mount a robust adaptive immune response and potentially contributing to disease progression. Differential ASFV infection profiles within the spleen were also detected, highlighting the diversity of ASFV cellular tropism. Further investigation into the innate-adaptive immune axis is needed to better understand its role in ASFV infection.

Effective immune defence and pathogen clearance requires coordination between innate and adaptive immune responses. However, virulent African swine fever virus (ASFV), which has a high case fatality rate in pigs, causes severe disease by exploiting multiple immune evasion strategies to suppress host responses. The global spread of Georgia2007/1 and its derivatives poses a significant threat to the pig industry and global food security. Although modified live virus vaccines for ASF exist, multiple safety concerns have restricted their use internationally. Conversely, subunit vaccine candidates have not matched the protective efficacy of modified live virus vaccines. This highlights the need to further investigate ASFV-induced immunopathology to support the development of next-generation ASF vaccines. Immune dynamics in whole blood and lymphoid tissues were examined over time after oronasal infection with Georgia 2007/1. CD4 ⁺ T cells, γδ-TCR ⁺ T cells and CD21 ⁺ B cells were impacted by lymphopenia, and initial immune activation was detected. However, as the disease progressed, impaired maintenance and depletion of adaptive immune cells, such as CD4 ⁺ T cells and professional antigen-presenting dendritic cells and macrophages was observed. This depletion of cells may have compromised the innate-adaptive immune axis, weakening host ability to mount a robust adaptive immune response and potentially contributing to disease progression. Differential ASFV infection profiles within the spleen were also detected, highlighting the diversity of ASFV cellular tropism. Further investigation into the innate-adaptive immune axis is needed to better understand its role in ASFV infection.