Levi R, Aboud-Pirak E, Leclerc C, Lowell G H, Arnon R
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Vaccine. 1995 Oct;13(14):1353-9. doi: 10.1016/0264-410x(94)00083-y.
Synthetic vaccines that are based on peptides representing immunogenic epitopes require a carrier molecule as well as an adjuvant in order to be effective. The choice of carriers or adjuvants approved for use in humans is very limited, and a considerable effort is devoted to develop new and efficient delivery systems. One of these vehicles utilizes preparations of outer membranes of meningococci, that form hydrophobic interactions, denoted proteosomes. Immunogenic proteins and peptides can be anchored to these proteosomes vesicles, which may serve as both carrier and adjuvant functions. In the present study we examined the ability of proteosomes to present epitopes of influenza, to elicit specific anti-influenza responses and to protect mice against viral challenge after intranasal immunization. Three influenza peptides were used--one corresponding to amino acid residues 91-108 of the haemagglutinin surface glycoprotein of H3 subtype, which comprises a B-cell epitope, and two from the internal nucleoprotein--a T-helper cell (Th) epitope (residues 55-69) and a cytotoxic T-lymphocyte (CTL) epitope (147-158). Mice were immunized intranasally (i.n.) with preparations containing each of the above epitopes, or various combinations thereof. The results obtained with this system demonstrate that influenza epitopes represented by synthetic peptides anchored to a proteosome carrier elicit both humoral and cellular specific immune responses, that can lead to partial protection of the mice from viral challenge. The importance of immunizing with vaccines containing both B- and T-cell peptide epitopes was emphasized by the demonstration that such vaccines elicited longer lasting immunity and led to more effective protection against influenza viral challenge.
基于代表免疫原性表位的肽的合成疫苗，为了有效发挥作用，需要载体分子和佐剂。被批准用于人类的载体或佐剂的选择非常有限，因此人们投入了大量精力来开发新的高效递送系统。其中一种载体利用脑膜炎球菌的外膜制剂，其形成疏水相互作用，称为蛋白酶体。免疫原性蛋白质和肽可以锚定在这些蛋白酶体囊泡上，这些囊泡可以同时发挥载体和佐剂的功能。在本研究中，我们检测了蛋白酶体在鼻内免疫后呈递流感表位、引发特异性抗流感反应以及保护小鼠免受病毒攻击的能力。使用了三种流感肽——一种对应于H3亚型血凝素表面糖蛋白的91 - 108位氨基酸残基，其包含一个B细胞表位，另外两种来自内部核蛋白——一个辅助性T细胞（Th）表位（55 - 69位残基）和一个细胞毒性T淋巴细胞（CTL）表位（147 - 158位残基）。用含有上述每种表位或其各种组合的制剂对小鼠进行鼻内免疫。用该系统获得的结果表明，锚定在蛋白酶体载体上的合成肽所代表的流感表位可引发体液和细胞特异性免疫反应，这可以使小鼠部分免受病毒攻击。含有B细胞和T细胞肽表位的疫苗引发了更持久的免疫力，并导致对流感病毒攻击的更有效保护，这突出了用此类疫苗进行免疫的重要性。
