| 摘要 |
A self-adjuvanting immunogenic composition comprising an immunogen comprising a lipopeptide cap (R2), a universal T helper sequence (R1) and an immunodominant Aß B cell epitope. The immunogen also comprises one or more linker sequences and/or polar charged amino acid sequences. The B cell epitope of each immunogen has an amino acid sequence located within the first 17 amino acids of SEQ ID NO: 1. The lipopeptide is a dipalmitoyl-S-glyceryl-cysteine or a tripalmitoyl-S-glyceryl cysteine or N-acetyl (dipalmitoyl-S-glyceryl cysteine), each with an optional neutral amino acid linker. Optional polar sequences of at least four charged polar amino acids enhance solubility of the immunogen and are located at the carboxy terminal end of R2, optionally flanked by neutral linker amino acids, or elsewhere in the immunogen. Such compositions, at surprisingly low dosages of less than 10 mg per subject, can induce anti-A/8 peptide antibodies with GMTs of 50,000 or greater than 1,000,000 when employed to immunize a mammalian subject, without any extrinsic adjuvant. |
