Towards an immunosense vaccine to prevent toxoplasmosis: Protective Toxoplasma gondii epitopes restricted by HLA-A*0201

Abstract

The ideal vaccine to protect against toxoplasmosis in humans would include antigens that elicit a protective T helper cell type 1 immune response, and generate long-lived IFN-γ-producing CD8 + T cells. Herein, we utilized a predictive algorithm to identify candidate HLA-A02 supertype epitopes from T. gondii proteins. Thirteen peptides elicited production of IFN-γ from PBMC of HLA-A02 supertype persons seropositive for T. gondii infection but not from seronegative controls. These peptides displayed high-affinity binding to HLA-A02 proteins. Immunization of HLA-A*0201 transgenic mice with these pooled peptides, with a universal CD4 + epitope peptide called PADRE, formulated with adjuvant GLA-SE, induced CD8 + T cell IFN-γ production and protected against parasite challenge. Peptides identified in this study provide candidates for inclusion in immunosense epitope-based vaccines.

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

“…These cells were processed and cryopreserved as described previously (3). ELISpot assays with human PBMCs used anti-human IFN-γ mAb (1-D1K) with biotinylated anti-human IFN-γ mAb (7B6-1) with 2 × 10 5 PBMCs per well (5,6). All antibodies and reagents used for ELISpot assays were from Mabtech.…”

“…The PBMC were plated in at least 3 replicate wells for each condition. Results were expressed as the number of spot-forming cells (SFCs) per 11 × 0 6 PBMCs. Epitope peptides.…”

“…Our recent work has focused on development of an epitope-based vaccine to prevent toxoplamosis to enhance host immunity by stimulating efficacious responses of CD4 + helper T lymphocytes (HTLs) and CD8 + IFN-γ-producing T lymphocytes (3-6) for humans. These CD8 + T cells recognize the octamer/nonamer peptides presented by HLA supermotif major histocompatibility complex class I (MHC-I) molecules on antigen presenting cells (APCs) in humans (3)(4)(5)(6). Considerable effort has been made to identify promising vaccine candidate antigens for Toxoplasma gondii…”

“…Using bioinformatic analyses, multiple predicted CD8 + epitopes of tachyzoite-and bradyzoite-specific antigens have recently entered our vaccine development pipeline (3)(4)(5)(6). Candidate amino acid sequences are from surface antigens (SAG1 and SUSA1) and secreted proteins, including dense granule proteins (GRA2, GRA3, GRA6, GRA7) and rhoptry proteins (ROP2, ROP16, ROP18).…”

“…Candidate amino acid sequences are from surface antigens (SAG1 and SUSA1) and secreted proteins, including dense granule proteins (GRA2, GRA3, GRA6, GRA7) and rhoptry proteins (ROP2, ROP16, ROP18). We reported in our previous studies CD8 + epitopes derived from these antigens that can be presented by HLA-A02, HLA-A03, and HLA-B*07 supermotif human MHC molecules (3)(4)(5)(6). These CD8 + T cell-restricted peptides -administered with a universal helper T cell epitope, PADRE, and adjuvants -elicit IFN-γ and reduce parasite burden in HLA-B*07:02, HLA-A*11:01, and HLA-A*02:01 transgenic mice.…”