CD205-targeted bispecific nanobody enhances antigen presentation and immune responses in FMDV

作者：Li Yang, Xin Sun, Luping Du, Zizheng Cai, Liting Hou, Qin Zhu, Jin Chen, Lu Yu, Xiuli Feng, Qisheng Zheng, Haiwei Cheng · 发表于：Veterinary Vaccine · 年份：2025 · DOI：10.1016/j.vetvac.2025.100131 · 被引用次数：4 · 研究领域：Immunotherapy and Immune Responses、Monoclonal and Polyclonal Antibodies Research、RNA Interference and Gene Delivery

ABSTRACT Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play a pivotal role in bridging innate and adaptive immunity, making them a central focus in vaccine development. As a C-type lectin receptor expressed on cDC1 and cDC2 subsets, CD205 facilitates receptor-mediated endocytosis, enabling antigen presentation through both MHC class I and class II pathways, which are critical for activating cytotoxic and helper T cells. In this study, we introduced a CD205-targeted bispecific nanobody (BiNb-CD205/FMDV) as a novel platform for enhancing antigen delivery and immune activation of foot-and-mouth disease virus (FMDV) in pigs. In vitro experiments demonstrated that BiNb-CD205/FMDV could bind efficiently to porcine bone marrow-derived dendritic cells (BMDCs) and show a strong colocalization with acidic organelles such as lysosome, indicating significantly enhancing antigen uptake and effective processing. In vivo immunization results revealed Nb4-Nb205 was effective at enhancing LPB-specific antibody titers, inducing enhanced CD4 + and CD8 + T cell responses. Elevated cytokine levels, including IFN-γ and IL-4 further supported robust immune activation, indicating a balanced Th1/Th2 response. Our results provide preliminary evidence for the feasibility of CD205-targeted bispecific nanobody platforms in enhancing antigen presentation and immune responses. This highlights the potential to expand targeted delivery to the field of animal epidemic diseases an...