The jawless vertebrates (agnathans or cyclostomes) are ancestral animals comprising lampreys and hagfishes, which are the only extant representatives. They possess an alternative adaptive immune system (AIS) that uses leucine-rich repeats (LRR)-based variable lymphocyte receptors (VLRs) instead of the immunoglobulin (Ig)-based antigen receptors of jawed vertebrates (gnathostomes). The five VLR types (VLRA-VLRE) are expressed on agnathan lymphocytes and functionally resemble lymphocyte antigen receptors. In particular, VLRB is functionally similar to the B cell receptor expressed and secreted by B-like lymphocytes as VLRB antibodies that bind antigens with high affinity and specificity. The potential repertoire scale of VLR-based antigen receptors is believed to be at least comparable to that of Ig-based systems. VLR proteins inherently possess characteristics that render them excellent candidates for biotechnological development, including tractability to recombinant approaches. In recent years, scientists have explored the biotechnological development and utility of VLRB proteins as alternatives to conventional mammalian antibodies. The VLRB antibody platform represents a non-traditional approach to generating a highly diverse repertoire of unique antibodies. In this review, we first describe some aspects of the biology of the AIS of the jawless vertebrates, which recognize antigens by means of unique receptors. We then summarize reports on the development of VLRB-based antibodies and their applications, particularly those from the inshore hagfish (Eptatretus burgeri) and their potential uses to address microbial diseases in aquaculture. Hagfish VLRB mAbs are being developed and improved, while obstacles to the advancement of the VLRB platform are being addressed to utilize VLRBs effectively as tools in immunology. Hence, mAbs for novel antigen targets are expected to emerge to provide new opportunities to tackle various scientific questions. We anticipate a greater interest in the agnathan AIS in general and particularly in the hagfish AIS for greater elucidation of the evolution of adaptive immunity and its applications to tackle microbial pathogens in farmed aquatic animals and beyond.

无颌脊椎动物（无颌类或环口类）是包括七鳃鳗和盲鳗在内的祖先动物，它们是现存的唯一代表。它们拥有另一种适应性免疫系统 (AIS)，该系统使用基于富含亮氨酸重复序列 (LRR) 的可变淋巴细胞受体 (VLR)，而不是有颌脊椎动物（颌口动物）基于免疫球蛋白 (Ig) 的抗原受体。五种 VLR 类型 (VLRA-VLRE) 在无颌淋巴细胞上表达，其功能类似于淋巴细胞抗原受体。特别是，VLRB在功能上与B样淋巴细胞表达和分泌的B细胞受体相似，作为VLRB抗体以高亲和力和特异性结合抗原。基于 VLR 的抗原受体的潜在库规模被认为至少与基于 Ig 的系统相当。 VLR 蛋白固有的特性使它们成为生物技术开发的优秀候选者，包括重组方法的易处理性。近年来，科学家们探索了 VLRB 蛋白作为传统哺乳动物抗体替代品的生物技术开发和效用。 VLRB 抗体平台代表了一种产生高度多样化的独特抗体库的非传统方法。在这篇综述中，我们首先描述了无颌脊椎动物 AIS 生物学的一些方面，它们通过独特的受体识别抗原。然后，我们总结了基于 VLRB 的抗体的开发及其应用的报告，特别是来自近岸盲鳗（Eptatretus Burgeri）的抗体及其在解决水产养殖中微生物疾病方面的潜在用途。 Hagfish VLRB mAb 正在开发和改进，同时正在解决 VLRB 平台发展的障碍，以有效利用 VLRB 作为免疫学工具。因此，针对新抗原靶点的单克隆抗体预计将出现，为解决各种科学问题提供新的机会。我们预计人们对无颌 AIS 更感兴趣，特别是盲鳗 AIS，以更好地阐明适应性免疫的进化及其在解决养殖水生动物及其他微生物病原体方面的应用。