Clough E R, Audibert F M, Barnwell J W, Schlesinger D H, Arnon R, Chedid L A
Infect Immun. 1985 Jun;48(3):839-42. doi: 10.1128/iai.48.3.839-842.1985.
A synthetic peptide whose sequence was derived from the circumsporozoite protein of Plasmodium knowlesi coupled to bovine gamma globulin has been shown to be immunogenic when administered with Freund complete adjuvant. The present experiments were designed to test the immunogenicity of the peptide when attached to a tetanus toxoid carrier and administered with alum or murabutide, both acceptable clinical adjuvants. In both cases, the use of an adjuvant increased the levels of circulating anti-peptide antibodies over those observed when no adjuvant was used. However, when the antisera were tested for reactivity with the native protein, animals of the group receiving the conjugate associated with murabutide always had titers greatly exceeding those observed in animals that received the conjugate with alum. Moreover, the sera of the murabutide-treated group were shown to be more active in eliciting shedding of the circumsporozoite protein than were sera of animals of the Freund complete adjuvant-treated group. The use of tetanus toxoid in secondary immunizations could be eliminated when the mice primed with peptide-tetanus toxoid and murabutide were boosted with a polymer of the peptide. The results indicate that the synthetic malarial peptide-tetanus toxoid conjugate is capable of stimulating high levels of biologically active antibodies only when administered with murabutide.
一种合成肽，其序列源自诺氏疟原虫环子孢子蛋白，并与牛γ球蛋白偶联，已证明与弗氏完全佐剂一起给药时具有免疫原性。本实验旨在测试该肽与破伤风类毒素载体连接并与明矾或murabutide（两种可接受的临床佐剂）一起给药时的免疫原性。在这两种情况下，使用佐剂都比不使用佐剂时观察到的循环抗肽抗体水平有所提高。然而，当检测抗血清与天然蛋白的反应性时，接受与murabutide相关偶联物的组中的动物的滴度总是大大超过接受与明矾偶联物的动物中观察到的滴度。此外，murabutide处理组的血清在引发环子孢子蛋白脱落方面比弗氏完全佐剂处理组动物的血清更具活性。当用肽聚合物对用肽 - 破伤风类毒素和murabutide进行初次免疫的小鼠进行加强免疫时，可以省去二次免疫中破伤风类毒素的使用。结果表明，合成疟疾肽 - 破伤风类毒素偶联物仅在与murabutide一起给药时才能刺激高水平的生物活性抗体。
