Francis M J, Hastings G Z, Brown F, McDermed J, Lu Y A, Tam J P
Department of Virology R & D, Wellcome Biotechnology Ltd, Beckenham, Kent, U.K.
Immunology. 1991 Jul;73(3):249-54.
The multiple antigenic peptide (MAP) system for presenting epitopes to the immune system has been studied with an immunogenic foot-and-mouth disease virus (FMDV) peptide comprising amino acids 141-160 of protein VP1. Neutralizing antibody responses known to protect guinea-pigs against challenge infection were obtained with a single inoculation of 0.8-4 micrograms of peptide, presented as an octamer or a tetramer, whereas 20 micrograms of a dimer were required to evoke a similar level of antibody. A monomeric preparation did not elicit measurable levels of neutralizing antibody at doses up to 20 micrograms. The octameric MAP was also immunogenic using an aluminum hydroxide adjuvant. Antibodies elicited by the octameric, tetrameric and dimeric constructs differed qualitatively in their reaction with sequences within the 141-160 peptide. Those against the octamer reacted poorly with peptides within the 141-160 sequence, whereas those elicited by the tetramer and dimer reacted preferentially with the peptides covering the N-terminal region. The levels of neutralizing antibody obtained with the octamer and tetramer compare favourably with those obtained when the FMDV peptide is attached to carrier proteins but are lower than those obtained when it is presented as part of a peptide-hepatitis B virus core particle. Nevertheless, the ability to elicit protective levels of neutralizing antibody without the use of a carrier protein would be a distinct advantage in the development of synthetic peptide vaccines.
用于向免疫系统呈递表位的多抗原肽(MAP)系统,已针对一种免疫原性口蹄疫病毒(FMDV)肽进行了研究,该肽包含VP1蛋白的141 - 160位氨基酸。以八聚体或四聚体形式呈现的0.8 - 4微克肽单次接种后,获得了已知能保护豚鼠抵抗攻击感染的中和抗体反应,而引发类似抗体水平则需要20微克的二聚体。剂量高达20微克的单体制剂未引发可测量水平的中和抗体。使用氢氧化铝佐剂时,八聚体MAP也具有免疫原性。由八聚体、四聚体和二聚体构建体引发的抗体,在与141 - 160肽内序列的反应上存在质的差异。针对八聚体的抗体与141 - 160序列内的肽反应较差,而由四聚体和二聚体引发的抗体则优先与覆盖N端区域的肽反应。八聚体和四聚体获得的中和抗体水平,与FMDV肽连接到载体蛋白上时获得的水平相比具有优势,但低于其作为肽 - 乙型肝炎病毒核心颗粒的一部分呈现时获得的水平。然而,在不使用载体蛋白的情况下引发具有保护水平的中和抗体的能力,在合成肽疫苗的开发中将是一个明显的优势。