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

Abstract

African Swine Fever Virus (ASFV) poses a serious threat to the pork industry worldwide; however, there is no safe vaccine or treatment available. The development of an efficacious subunit vaccine will require the identification of protective antigens. The ASFV pp220 polyprotein is essential for virus structural integrity. This polyprotein is processed to generate p5, p34, p14, p37, and p150 individual proteins. Immunization of pigs with a cocktail of adenoviruses expressing the proteins induced significant IgG, IFN-γ-secreting cells, and cytotoxic T lymphocyte responses. Four predicted SLA-I binding nonamer peptides, namely p34161−169, p37859−867, p1501363−1371, and p1501463−1471, recalled strong IFN-γ+ PBMC and splenocyte responses. Notably, peptide p34161−169 was recognized by PBMCs isolated from 7/10 pigs and by splenocytes isolated from 8/10 pigs. Peptides p37859−867 and p1501363−1371 stimulated recall IFN-γ+ responses in PBMCs and splenocytes isolated from 8/10 pigs, whereas peptide p1501463−1471 recalled responses in PBMCs and splenocytes isolated from 7/10 to 9/10 pigs, respectively. The results demonstrate that the pp220 polyprotein contains multiple epitopes that induce robust immune responses in pigs. Importantly, these epitopes are 100% conserved among different ASFV genotypes and were predicted to bind multiple SLA-I alleles. The outcomes suggest that pp220 is a promising candidate for inclusion in a prototype subunit vaccine.

VirusImmu: a novel ensemble machine learning approach for viral immunogenicity prediction

“…As there is no effective vaccine or treatment for ASFV, it is required to identify protective antigens. ASFV pp220 polyprotein essential for virus structural integrity [27] was found containing epitopes that can induce robust immune responses in pigs, suggesting it will be promising candidate in vaccine development [27].…”

Immunoinformatics-guided approach for designing a pan-proteome multi-epitope subunit vaccine against African swine fever virus

“…However, the results revealed that a greater number of epitopes from other protein sources exhibited higher immunogenicity than epitopes found on these structural proteins. Four out of the ten protein sources of the T-cell epitopes in the study, including polyprotein pp220 (CP2475L) 27 , 71 , 72 , guanylyltransferase (NP868R) 22 , helicase/primase (F1055L) 72 , and MGF 360-11L 20 , 72 , induced T-cell responses against ASFV in in vitro experiments. Meanwhile, all four protein sources of the LBL epitopes—minor capsid protein p49 (B438L) 73 , envelope protein p22 22 , 74 , transmembrane protein (C257) 22 , and major capsid protein p72 (B646L) 22 , 73 – 76 have shown positive antibody response against the virus in in vitro studies.…”

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

“…pp220 polyprotein contains at least four T cell epitopes, which are located at position 161–169, 859–867, 1363–1371 and 1463–1471. Strong IFN-γ responses can be induced in domestic pigs by immunization with pp220 ( Zajac et al, 2022 ). Previous studies have predicted that epitopes IADAINQEF, QIYKTLLEY and SLYPTQFDY (located in pp220) were highly conserved T cell epitopes in ASFV genome and could therefore be a promising candidate for vaccine development ( Herrera and Bisa, 2021 ).…”