Identification and Immunogenicity of African Swine Fever Virus Antigens

Abstract

African swine fever (ASF) is a lethal haemorrhagic disease of domestic pigs for which there is no vaccine. Strains of the virus with reduced virulence can provide protection against related virulent strains of ASFV, but protection is not 100% and there are concerns about the safety profile of such viruses. However, they provide a useful tool for understanding the immune response to ASFV and previous studies using the low virulent isolate OUR T88/3 have shown that CD8+ cells are crucial for protection. In order to develop a vaccine that stimulates an effective anti-ASFV T-cell response we need to know which of the >150 viral proteins are recognized by the cellular immune response. Therefore, we used a gamma interferon ELIspot assay to screen for viral proteins recognized by lymphocytes from ASF-immune pigs using peptides corresponding to 133 proteins predicted to be encoded by OUR T88/3. Eighteen antigens that were recognized by ASFV-specific lymphocytes were then incorporated into adenovirus and MVA vectors, which were used in immunization and challenge experiments in pigs. We present a systematic characterization of the cellular immune response to this devastating disease and identify proteins capable of inducing ASFV-specific cellular and humoral immune responses in pigs. Pools of viral vectors expressing these genes did not protect animals from severe disease, but did reduce viremia in a proportion of pigs following ASFV challenge.

Classification of multigene families of African swine fever viruses

“…This may be related to the diverse functions of MGF proteins reported in previous studies (L. Dixon, Islam, Nash, & Reis, 2019; Netherton et al, 2019). For example, it is reported that the MGF proteins were associated with the virulence, antigenicity and immune escape of ASFVs (Burrage, Lu, Neilan, Rock, & Zsak, 2004; Golding et al, 2016).…”

The genetic variation landscape of African swine fever virus reveals frequent positive selection and adaptive flexibility

“…We ascertain the genetic properties of the genes with positive diversifying selection or selective sweep by calculating population prevalence frequencies and pair-wise amino acid divergence of the genes and doing comparison with three gene categories cataloged from other studies: (i) the non-antigenic conserved structural proteins without positive selection (32), (ii) the antigen proteins eliciting immunological responses in immunoassay experiments (40)(41)(42), (iii) the proteins previously shown to be involved in host cell interactions (10,43) ( Figure 4 and Table S6). A non-uniform population prevalence and higher level of sequence variability are observed in the candidate genes under putative positive diversifying selection in comparison with the category of (i) conserved structural proteins and (ii) antigenic proteins, but not with the gene category (iii) involved in host cell interactions (two-sided Mann-Whitney U-test, Figure 4a…”

Bovine Herpesvirus-4-Vectored Delivery of Nipah Virus Glycoproteins Enhances T Cell Immunogenicity in Pigs

“…The CD8α chain forms part of the heterodimer coreceptor for TcR engagement with MHC class I-peptide complexes. Initially thought to be a mechanism to aid peripheral tolerance, CD8 down-regulation on primed/activated T cell populations has been described in both humans and mice in a variety of contexts including in response to infection [81][82][83][84]. We therefore speculate that a combination of the magnitude of the BoHV-4 vector induced T cell response and the high concentrations of peptides used in the recall assay may have contributed to the decreased CD3/CD8α surface expression.…”