Clough E R, Jolivet M, Audibert F, Barnwell J W, Schlesinger D H, Chedid L
Biochem Biophys Res Commun. 1985 Aug 30;131(1):70-6. doi: 10.1016/0006-291x(85)91771-1.
A synthetic peptide (pep) representing a portion of the Plasmodium knowlesi circumsporozoite protein attached to a tetanus toxoid (TT) carrier, has been shown to be immunogenic when delivered in saline with derivatives of the synthetic adjuvant, muramyl dipeptide (MDP). The present study was designed to determine if the degree of substitution of pep and of MDP derivatives on the tetanus toxoid (TT) carrier, as well as the choice of MDP derivative used play a role in determining anti-pep and anti-TT antibody levels. One of the MDP derivatives used in the conjugates was epsilon-amino-caproic Murabutide, since Murabutide which is currently in clinical trials cannot be conjugated. The results show that low doses of this derivative coupled with pep on TT can be used to stimulate high levels of circulating anti-pep antibodies without augmenting the anti-carrier response. In addition, anti-pep antibodies elicited in response to one of the conjugates were biologically active since they produced shedding of the circumsporozoite coat of live parasites.
一种代表诺氏疟原虫环子孢子蛋白一部分的合成肽(pep)与破伤风类毒素(TT)载体相连,当与合成佐剂胞壁酰二肽(MDP)的衍生物一起在盐溶液中递送时,已显示具有免疫原性。本研究旨在确定合成肽(pep)和MDP衍生物在破伤风类毒素(TT)载体上的取代程度,以及所用MDP衍生物的选择是否在决定抗pep和抗TT抗体水平方面发挥作用。缀合物中使用的一种MDP衍生物是ε-氨基己酰基Murabutide,因为目前正在进行临床试验的Murabutide不能进行缀合。结果表明,低剂量的这种与TT上的pep偶联的衍生物可用于刺激高水平的循环抗pep抗体,而不会增强抗载体反应。此外,针对其中一种缀合物产生的抗pep抗体具有生物活性,因为它们能使活寄生虫的环子孢子外衣脱落。