Arnon R, Sela M, Parant M, Chedid L
Proc Natl Acad Sci U S A. 1980 Nov;77(11):6769-72. doi: 10.1073/pnas.77.11.6769.
In a previous study we demonstrated that antiviral response against the coliphage MS-2 can be elicited by immunization with a synthetic antigen consisting of a conjugate (P2-A -- L) of a synthetic fragment (P2) of the virus coat protein attached to a synthetic polymeric carrier. The antiviral response was induced when the antigen was administered in complete Freund's adjuvant or when it was administered in incomplete adjuvant, provided that a peptidoglycan was covalently attached to it. In the present study we demonstrate the adjuvant effect of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in this system. Immunization with a mixture of MDP and P2-A -- L brought about only slight enhancement in the titer of neutralizing antibodies, as compared to the immunization with P2-A -- L in saline. The best results were achieved when the MDP was chemically conjugated to P2-A -- L. This completely synthetic material, when administered in aqueous solution, yielded highly inactivating antiserum with a titer similar to that obtained with complete Freund's adjuvant in the absence of MDP. MDP-P2-A -- L elicited also a humoral immune response to MDP, but with much lower titer than that induced by complete Freund's adjuvant containing P2-A -- L only. It was also observed that the capacity of MDP-P2-A -- L to increase resistance against infection was more than a 100-fold greater than that of unconjugated MDP.
在先前的一项研究中,我们证明,用一种合成抗原进行免疫可引发针对大肠杆菌噬菌体MS-2的抗病毒反应,该合成抗原由附着在合成聚合物载体上的病毒衣壳蛋白合成片段(P2)的缀合物(P2-A-L)组成。当抗原在完全弗氏佐剂中给药时,或者当它在不完全佐剂中给药时(前提是肽聚糖与之共价连接),均可诱导抗病毒反应。在本研究中,我们证明了N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺(MDP)在该系统中的佐剂作用。与在盐水中用P2-A-L免疫相比,用MDP和P2-A-L的混合物免疫仅使中和抗体滴度略有提高。当MDP与P2-A-L化学偶联时,可获得最佳结果。这种完全合成的材料在水溶液中给药时,可产生高效灭活抗血清,其滴度与在无MDP情况下用完全弗氏佐剂获得的滴度相似。MDP-P2-A-L也引发了对MDP的体液免疫反应,但其滴度远低于仅含P2-A-L的完全弗氏佐剂所诱导的滴度。还观察到,MDP-P2-A-L增加抗感染能力的程度比未偶联的MDP大100倍以上。