近日，美国斯坦福大学Michael A. Fischbach及其研究小组发现并工程化对一种显著皮肤共生菌的抗体反应。相关论文于2024年12月11日在线发表在《自然》杂志上。

研究人员表示，普遍存在的皮肤定植菌表皮葡萄球菌（Staphylococcus epidermidis）在没有感染的情况下，会提前诱导CD8⁺ T细胞反应。然而，这种抗共生菌免疫程序的范围和目的尚不明确，限制了我们将其用于治疗的能力。

研究人员展示了这一定植菌还诱导了一种强效、持久且特异的抗体反应，这种反应在人类和非人类灵长类动物中都很保守。通过一系列表皮葡萄球菌细胞壁突变体的研究，研究人员发现细胞表面蛋白Aap是主要的靶点。通过将小鼠定植一种表皮葡萄球菌菌株，在其中Aap的平行β螺旋结构域被破伤风毒素C片段替代，研究人员诱导了强效的中和抗体反应，保护小鼠免受致死性感染。类似的表皮葡萄球菌菌株，表达Aap-SpyCatcher嵌合体，可以与重组免疫原结合；在生理性定植条件下，所产生的标记共生菌能够诱导高抗体滴度，包括在鼻腔和肺部粘膜中的强IgA反应。

因此，针对常见皮肤定植菌的免疫反应涉及协调的T细胞和B细胞反应，后者可以被重新定向用于抗病原体，进而作为一种新的局部疫苗接种方式。

附：英文原文

Title: Discovery and engineering of the antibody response to a prominent skin commensal

Author: Bousbaine, Djenet, Bauman, Katherine D., Chen, Y. Erin, Lalgudi, Pranav V., Nguyen, Tam T. D., Swenson, Joyce M., Yu, Victor K., Tsang, Eunice, Conlan, Sean, Li, David B., Jbara, Amina, Zhao, Aishan, Naziripour, Arash, Veinbachs, Alessandra, Lee, Yu E., Phung, Jennie L., Dimas, Alex, Jain, Sunit, Meng, Xiandong, Pham, Thi Phuong Thao, McLaughlin, Martin I., Barkal, Layla J., Gribonika, Inta, Van Rompay, Koen K. A., Kong, Heidi H., Segre, Julie A., Belkaid, Yasmine, Barnes, Christopher O., Fischbach, Michael A.

Issue&Volume: 2024-12-11

Abstract: The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8+ T cell response pre-emptively, in the absence of an infection1. However, the scope and purpose of this anti-commensal immune program are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable, and specific antibody response that is conserved in humans and non-human primates. A series of S. epidermidis cell-wall mutants revealed that the cell surface protein Aap is a predominant target. By colonizing mice with a strain of S. epidermidis in which the parallel β-helix domain of Aap is replaced by tetanus toxin fragment C, we elicit a potent neutralizing antibody response that protects mice against a lethal challenge. A similar strain of S. epidermidis expressing an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits high antibody titers under conditions of physiologic colonization, including a robust IgA response in the nasal and pulmonary mucosa. Thus, immunity to a common skin colonist involves a coordinated T and B cell response, the latter of which can be redirected against pathogens as a novel form of topical vaccination.

DOI: 10.1038/s41586-024-08489-4

Source: https://www.nature.com/articles/s41586-024-08489-4