Pugholm L H, Petersen L R, Søndergaard E K L, Varming K, Agger R
Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
Laboratory of Immunology, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Scand J Immunol. 2015 Dec;82(6):515-22. doi: 10.1111/sji.12387.
Dendritic cells (DCs) are superior in their ability to induce and control adaptive immune responses. These qualities have motivated the hypothesis that targeted delivery of antigen to DCs in vivo may be an effective way of enhancing immunization. Recent results show that antigen targeted to certain DC surface molecules may indeed induce robust immune responses. Targeting of antigen to DCs can be accomplished by the means of monoclonal antibodies. This study compared the humoral responses induced in mice by in vivo targeting of DCs using monoclonal antibodies specific for CD11c, CD36, CD205, Clec6A, Clec7A, Clec9A, Siglec-H and PDC-TREM. The results demonstrate that antigen delivery to different targets on DCs in vivo gives rise to humoral responses that differ in strength. Targeting of antigen to CD11c, CD36, CD205, Clec6A, Clec7A and PDC-TREM induced significantly stronger antibody responses compared to non-targeted isotype-matched controls. Targeting of Clec9A and Siglec-H did not lead to efficient antibody responses, which may be due to unfavourable properties of the targeting antibody, in which case, other antibodies with the same specificity might elicit a different outcome. Anti-CD11c was additionally used for elucidating the impact of the route of vaccination, and the results showed only minor differences between the antibody responses induced after immunization either s.c., i.v. or i.p. Altogether, these data show that targeting of different surface molecules on DCs result in very different antibody responses and that, even in the absence of adjuvants, strong humoral responses was induced.
树突状细胞(DCs)在诱导和控制适应性免疫反应方面能力卓越。这些特性促使人们提出这样的假说:在体内将抗原靶向递送至DCs可能是增强免疫的有效方法。近期结果表明,靶向某些DC表面分子的抗原确实可诱导强烈的免疫反应。通过单克隆抗体可实现将抗原靶向递送至DCs。本研究比较了使用针对CD11c、CD36、CD205、Clec6A、Clec7A、Clec9A、Siglec-H和PDC-TREM的单克隆抗体在体内靶向DCs后在小鼠中诱导的体液免疫反应。结果表明,在体内将抗原递送至DCs上的不同靶点会引发强度不同的体液免疫反应。与非靶向的同型对照相比,将抗原靶向递送至CD11c、CD36、CD205、Clec6A、Clec7A和PDC-TREM可诱导明显更强的抗体反应。将抗原靶向递送至Clec9A和Siglec-H并未导致有效的抗体反应,这可能是由于靶向抗体的不良特性所致,在这种情况下,具有相同特异性的其他抗体可能会产生不同的结果。此外,抗CD11c还用于阐明疫苗接种途径的影响,结果显示皮下、静脉内或腹腔内免疫后诱导的抗体反应之间仅存在微小差异。总之,这些数据表明,靶向DCs上不同的表面分子会导致非常不同的抗体反应,并且即使在没有佐剂的情况下,也能诱导强烈的体液免疫反应。