A virosome-mimotope approach to synthetic vaccine design and optimization:: Synthesis, conformation, and immune recognition of a potential malaria-vaccine candidate
A virosome-mimotope approach to synthetic vaccine design and optimization:: Synthesis, conformation, and immune recognition of a potential malaria-vaccine candidate
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DOI：
10.1002/anie.200250348
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Robinson, JA
中科院分区：
文献类型：
--
作者：
Pfeiffer, B;Peduzzi, E;Robinson, JA
迄今为止，生产抗疟疾寄生虫恶性疟原虫疫苗的尝试取得了有限的成功。用于刺激保护性抗体反应的分子通常在人类中仅显示出较差的功效。[1]合成肽是疫苗设计的有吸引力的靶标，因为它们易于合成并且能够靶向特异性抗原，但是它们的使用遭受了许多缺点。[2]这些包括不良的免疫原性和构象表位的不良模拟性、不良的蛋白水解稳定性以及缺乏合适的人类递送系统。为了增强免疫原性，短肽通常与载体蛋白偶联，然后与免疫刺激佐剂一起注射，免疫刺激佐剂对人类来说通常是明矾吸收的抗原。我们在此介绍一种替代方法合成疫苗的设计和优化（见图1），其中涉及使用肽模拟物传递到免疫系统的免疫增强重组流感病毒体（IRIV）的表面。[3]IRIV类似于脂质体，但含有流感衍生的膜结合血凝素和神经氨酸酶，其赋予融合活性并促进抗原递送至免疫活性细胞。IRIV用于疫苗递送的潜在优势包括其融合活性、分子定义抗原的表面展示以及与动物（例如小鼠）和人类的相容性。[4]基于结构-活性关系的连续轮模拟物优化可以理想地产生疫苗候选物，其在适当的临床前分析之后，可以在人体中测试。
Attempts to produce a vaccine against the malaria parasite Plasmodium falciparum have so far met with limited success. The molecules used to stimulate a protective antibody response have in general shown only poor efficacy in humans.[1] Synthetic peptides are attractive targets for vaccine design, as they are readily synthesized and are able to target specific antigens, but their use has suffered a number of drawbacks.[2] These include poor immunogenicity and poor mimicry of conformational epitopes, poor proteolytic stability, and the lack of a suitable delivery system in humans. To enhance immunogenicity, short peptides are usually coupled to a carrier protein and then injected together with an immunostimulatory adjuvant, which for humans is typically an alum-absorbed antigen.We introduce herein an alternative approach to syntheticvaccine design and optimization (see Figure1), which involves the use of peptidomimetics delivered to the immune system on the surface of immunopotentiating reconstituted influenza virosomes (IRIVs).[3] The IRIVs are similar to liposomes, but contain influenza-derived, membrane-bound hemagglutinin and neuraminidase, which impart fusogenic activity and facilitate antigen delivery to immunocompetent cells. The potential advantages of IRIVs for vaccine delivery include their fusogenic activity, the surface display of molecularly defined antigens, and compatibility with both animals (eg mice) and humans.[4] Sequential rounds of mimetic optimization based on structure–activity relationships may ideally lead to vaccine candidates, which after appropriate preclinical profiling, can be tested in human