M448R and MGF505-7R: Two African Swine Fever Virus Antigens Commonly Recognized by ASFV-Specific T-Cells and with Protective Potential

Abstract

African swine fever (ASF) is today′s number one threat for the global swine industry. Neither commercial vaccine nor treatment is available against ASF and, thus far, only live attenuated viruses (LAV) have provided robust protection against lethal ASF virus (ASFV) challenge infections. Identification of ASFV proteins inducing protective immune responses is one of the major challenges to develop safer and efficient subunit vaccines. Immunopeptidomic studies recently performed in our laboratory allowed identifying ASFV antigens recognized by ASFV-specific CD8+ T-cells. Here, we used data from the SLAI-peptide repertoire presented by a single set of ASFV-infected porcine alveolar macrophages to generate a complex DNA vaccine composed by 15 plasmids encoding the individual peptide-bearing ORFs. DNA vaccine priming improved the protection afforded by a suboptimal dose of the BA71ΔCD2 LAV given as booster vaccination, against Georgia2007/1 lethal challenge. Interestingly, M448R was the only protein promiscuously recognized by the induced ASFV-specific T-cells. Furthermore, priming pigs with DNA plasmids encoding M488R and MGF505-7R, a CD8+ T-cell antigen previously described, confirmed these two proteins as T-cell antigens with protective potential. These studies might be useful to pave the road for designing safe and more efficient vaccine formulations in the future.

Adenovirus-Vectored African Swine Fever Virus pp220 Induces Robust Antibody, IFN-γ, and CTL Responses in Pigs

“…Future challenge studies will determine whether these peptides are also CTL epitopes produced from natural infection and whether they play a role in protection. The peptide ITKTFVNNI (number 68 in Table 2 ) was also previously identified by Bosch-Camos et al and assessed for immunogenicity in pigs when expressed using a plasmid vector; however, it did not elicit an immune response ( 94 ). More recent prediction data indicated peptides IADAINQEF, QIYKTLLEY, and SLYPTQFDY (numbers 2, 4-5 in Table 2 ) which are highly conserved cytotoxic T-cell epitopes in the ASFV genome ( 92 ).…”

Adaptive Cellular Immunity against African Swine Fever Virus Infections

“…Antigenic regions and individual epitopes have been identified in a number of ASFV proteins through a combination of fine mapping or bioinformatic-guided discovery with peptides or by eluting peptides directly from SLAs on the surface of infected cells [75,139,143,144]. Peptide mapping identified two regions within the EP153R protein and four within the EP402R/CD2v protein using IFNγ ELIspot [144].…”

African Swine Fever Virus A528R Inhibits TLR8 Mediated NF-κB Activity by Targeting p65 Activation and Nuclear Translocation

“…A528R-deleted ASFV had better IFN inducibility than wild-type ASFV and was fully attenuated in swine. The A528R gene, conserved across ASFV strains, has been identified as a common ASFV-specific T cell determinant and it has also been identified as a candidate to be included in future complex vaccine formulations [12]. It was initially identified as the inhibitor of poly I:C mediated IRF3 and NF-κB signaling, as well as type I IFN mediated signaling [13].…”