McCormick A L, Thomas M S, Heath A W
Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom.
J Infect Dis. 2001 Dec 1;184(11):1423-30. doi: 10.1086/324371. Epub 2001 Nov 13.
Cytokines, including interferon (IFN)-gamma, can be effective immunologic adjuvants but often lack the potency of other, more reactogenic compounds. On the basis of the observation that attachment of IFN-gamma to antigen could further enhance its adjuvanticity, a chimeric protein involving IFN-gamma and gp120 of human immunodeficiency virus was produced, using varying lengths of amino acid linkers between the two moieties. All resultant fusion proteins appeared to be dimerized, but full IFN-gamma biological activity was present only with the longest, 34-aa linker. Immunization with the fusion protein gave rise to enhanced primary antibody responses to gp120, particularly of the IgG2a subclass. In addition, both T cell proliferation and IFN-gamma production in response to antigen were strongly enhanced by primary immunization with the fusion protein. IFN-gamma fused to antigen is a more potent adjuvant for Th1-like responses than is IFN-gamma mixed with antigen.
细胞因子，包括干扰素（IFN）-γ，可作为有效的免疫佐剂，但往往缺乏其他更具反应原性的化合物的效力。基于IFN-γ与抗原结合可进一步增强其佐剂活性这一观察结果，制备了一种包含IFN-γ和人类免疫缺陷病毒gp120的嵌合蛋白，在两个部分之间使用了不同长度的氨基酸接头。所有产生的融合蛋白似乎都形成了二聚体，但只有最长的34个氨基酸的接头存在完整的IFN-γ生物学活性。用融合蛋白免疫可增强对gp120的初次抗体反应，尤其是IgG2a亚类。此外，初次用融合蛋白免疫可强烈增强抗原刺激下的T细胞增殖和IFN-γ产生。与抗原混合的IFN-γ相比，与抗原融合的IFN-γ是一种对Th1样反应更有效的佐剂。
