Olszewska W, Obeid O E, Steward M W
The Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
Virology. 2000 Jun 20;272(1):98-105. doi: 10.1006/viro.2000.0285.
Synthetic peptides mimicking a conformational B-cell epitope (M2) of the measles virus fusion protein (MVF) were used for the immunization of BALB/c mice and the anti-peptide and anti-virus antibody titers induced were compared. Of the panel of tested peptides, a chimeric peptide consisting of two copies of a T-helper epitope (residues 288-302 of MVF) and one copy of the mimotope M2 (TTM2) and a multiple antigen peptide with eight copies of M2 (MAP-M2) induced the highest titers of anti-M2 and anti-MV antibodies. Furthermore, peptides TTM2 and MAP-M2 induced antibodies with highest affinity for the mimotope and highest avidity for measles virus. Immunization with the MAP-M2 construct induced high titers of high-affinity anti-M2 antibody despite the absence of a T-helper epitope, and lymphocyte proliferation data suggest that the addition of M2 to the MAP resulted in the generation of a structure capable of stimulating T-cell help. Sera with anti-M2 reactivity were pooled according to affinity values for binding to M2, and high- and low-affinity pools were tested for their ability to prevent MV-induced encephalitis in a mouse model. The high-affinity serum pool conferred protection in 100% of mice, whereas the lower affinity pool conferred protection to only 50% of animals. These results indicate the potential of mimotopes for use as synthetic peptide immunogens and highlight the importance of designing vaccines to induce antibodies of high affinity.
使用模拟麻疹病毒融合蛋白（MVF）构象性B细胞表位（M2）的合成肽对BALB/c小鼠进行免疫，并比较诱导产生的抗肽和抗病毒抗体滴度。在一组测试肽中，由两个拷贝的T辅助表位（MVF的288 - 302位氨基酸）和一个拷贝的模拟表位M2组成的嵌合肽（TTM2）以及含有八个拷贝M2的多抗原肽（MAP-M2）诱导产生了最高滴度的抗M2和抗MV抗体。此外，肽TTM2和MAP-M2诱导产生的抗体对模拟表位具有最高亲和力，对麻疹病毒具有最高亲合力。尽管缺乏T辅助表位，但用MAP-M2构建体免疫仍诱导产生了高滴度的高亲和力抗M2抗体，淋巴细胞增殖数据表明，向MAP中添加M2导致产生了一种能够刺激T细胞辅助的结构。根据与M2结合的亲和力值汇集具有抗M2反应性的血清，并在小鼠模型中测试高亲和力和低亲和力血清库预防MV诱导的脑炎的能力。高亲和力血清库使100%的小鼠得到保护，而低亲和力血清库仅使50%的动物得到保护。这些结果表明模拟表位作为合成肽免疫原的潜力，并突出了设计疫苗以诱导高亲和力抗体的重要性。
