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对疟原虫红细胞前期的有效免疫预防需要有一种能诱导各种遗传背景个体的体液和细胞免疫的疫苗。为了使合成肽疟疾疫苗达到这个要求,必须克服遗传限制、肽化学、佐剂配方和制品的理化性质等问题。现已合成的5种候选多肟疫苗,是把恶性疟原虫环子孢子(CS)蛋白的纯化肽表位通过肟键连接到一个分支模板上。作者将CS蛋白上能诱导B细胞和T1细胞应答的重复表位构建成四支链双表位(T1B)_4,将(T1B)_4与T〔由CS蛋白C末端的第326-345位氨基酸构成的含广泛T辅助性(Th)细胞表位的T细胞表位〕连接构成三表位的(T1BT)_4,它能诱导不同遗传背景小鼠产生强Th细胞应答。合成佐剂是三棕榈酰-S-甘油半胱氨酸(Pam3Cys)。
Effective immune prophylaxis against the pre-erythrocytic stage of the malaria parasite requires a vaccine that induces humoral and cellular immunity in individuals of various genetic backgrounds. In order to meet this requirement for synthetic peptide malaria vaccines, genetic limitations, peptide chemistry, adjuvant formulations, and physical and chemical properties of the product must be overcome. The five candidate polyoxime vaccines that have been synthesized are those that link the purified peptide epitope of Plasmodium falciparum circumsporozoite (CS) protein to a branched template via an oxime bond. The authors constructed a repetitive epitope on CS protein that induces B-cell and T1 cell responses as a four-branched double-epitope (T1B) _4, combining (T1B) _4 with T [consisting of residues 326-345 at the C terminus of the CS protein T-cell epitopes containing extensive T-helper (Th) cell epitopes linked to the (T1BT) _4 triple epitope that induced strong Th cell responses in different genetic background mice. The synthetic adjuvant is tripalmitoyl-S-glyceryl cysteine (Pam3Cys).