申请人:MBF Therapeutics, Inc.
公开号:US11130787B2
公开(公告)日:2021-09-28
This invention provides new compositions comprising nucleotide sequence(s) encoding alphaherpesvirus glycoprotein D protein(s) (gDP(s)) and antigen(s) that induce immune responses. Such sequences typically encode gDP:antigen fusion proteins and typically also include feature(s) that significantly enhance immune responses such as (a) sequences encoding ITIC signal transducing adaptor proteins, e.g., SLAM-associated proteins (SAPs), Ewing's sarcoma-associated transcript 2 proteins, or both, or non-gDP checkpoint inhibitor(s); (b) sequences encoding antigen-associated targeting sequences, e.g., polyubiquitin sequences; (c) deimmunized/modified antigen-encoding sequences; (d) gDP(s) with modified sequence(s); (e) expression-enhancing introns; (f) transfection-facilitating agents; or (g) combinations thereof. Methods of using such constructs to induce immune responses and other methods and compositions also are provided, including methods of using such constructs in animals not known to express Herpesvirus entry mediator (HVEM) receptors (e.g., pigs), animals not under disease agent-associated checkpoint inhibition, and other contexts.
本发明提供了由编码α-疱疹病毒糖蛋白D蛋白(gDP)的核苷酸序列和诱导免疫反应的抗原组成的新组合物。这些序列通常编码 gDP:抗原融合蛋白,通常还包括能显著增强免疫应答的特征,如 (a) 编码 ITIC 信号转导适配蛋白的序列,如 SLAM 相关蛋白、SLAM相关蛋白(SAPs)、尤文肉瘤相关转录本2蛋白或两者,或非gDP检查点抑制剂;(b)编码抗原相关靶向序列的序列,如(c) 去免疫/修饰的抗原编码序列;(d) 具有修饰序列的 gDP;(e) 表达增强内含子;(f) 转染促进剂;或 (g) 其组合。还提供了使用此类构建体诱导免疫应答的方法以及其他方法和组合物,包括在不表达疱疹病毒进入介质(HVEM)受体的动物(如猪)、未受到疾病制剂相关检查点抑制的动物以及其他情况下使用此类构建体的方法。