Nardin E H, Calvo-Calle J M, Oliveira G A, Clavijo P, Nussenzweig R, Simon R, Zeng W, Rose K
Department of Medical and Molecular Parasitology, New York University School of Medicine, NY 10010, USA.
Vaccine. 1998 Apr;16(6):590-600. doi: 10.1016/s0264-410x(97)00238-7.
Effective immunoprophylaxis directed against the pre-erythrocytic stages of the malaria parasite requires a vaccine that can elicit humoral and cell mediated immunity in individuals of diverse genetic background. In order for a synthetic peptide malaria vaccine to meet these requirements, problems associated with genetic restriction, peptide chemistry, adjuvant formulation and physiochemical characterization of the final synthetic vaccine product must first be overcome. To address these issues, five polyoxime vaccine candidates have been constructed by ligating purified peptide epitopes of the P. falciparum CS protein to a branched template via oxime bonds. All five constructs, including two based on templates containing the synthetic adjuvant tripalmitoyl-S-glyceryl cysteine (Pam3Cys), were of sufficient purity for characterization by mass spectrometry. The immunogenicity of the malaria polyoximes in different murine strains was compared to that of multiple antigen peptide (MAP) constructs synthesized by standard step-wise synthesis. A tri-epitope polyoxime-Pam3Cys construct, based on the repeats and a universal T-cell epitope that contains both helper and CTL epitopes of the CS protein, was shown to be a precisely-defined synthetic malaria vaccine candidate that was highly immunogenic in murine strains of diverse H-2 haplotypes.
针对疟原虫红细胞前期阶段的有效免疫预防需要一种能够在不同遗传背景个体中引发体液免疫和细胞介导免疫的疫苗。为了使合成肽疟疾疫苗满足这些要求，必须首先克服与遗传限制、肽化学、佐剂配方以及最终合成疫苗产品的物理化学特性相关的问题。为了解决这些问题，通过肟键将恶性疟原虫环子孢子蛋白（CS蛋白）的纯化肽表位连接到一个分支模板上，构建了五种聚肟疫苗候选物。所有五种构建体，包括两种基于含有合成佐剂三棕榈酰 - S - 甘油基半胱氨酸（Pam3Cys）的模板的构建体，纯度都足以通过质谱进行表征。将疟疾聚肟在不同小鼠品系中的免疫原性与通过标准逐步合成法合成的多抗原肽（MAP）构建体的免疫原性进行了比较。一种基于CS蛋白的重复序列以及包含辅助性T细胞和细胞毒性T淋巴细胞表位的通用T细胞表位的三表位聚肟 - Pam3Cys构建体，被证明是一种精确界定的合成疟疾疫苗候选物，在不同H - 2单倍型的小鼠品系中具有高度免疫原性。
