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.

在没有感染的情况下，无处不在的皮肤定植者表皮葡萄球菌会先发制人地引发 CD8⁺ T 细胞反应¹。然而，这种抗共生免疫计划的范围和目的并不明确，限制了我们在治疗中利用它的能力。在这里，我们表明这种定殖者还诱导了一种有效、持久和特异性的抗体反应，这种反应在人类和非人类灵长类动物中是保守的。一系列表皮葡萄球菌细胞壁突变体显示，细胞表面蛋白 Aap 是主要靶标。通过用表皮葡萄球菌菌株定植小鼠，其中 Aap 的平行 β-螺旋结构域被破伤风毒素片段 C 取代，我们引发了有效的中和抗体反应，保护小鼠免受致命挑战。表达 Aap-SpyCatcher 嵌合体的类似表皮链球菌菌株可以与重组免疫原偶联;所得标记的共生体在生理定植条件下引发高抗体滴度，包括鼻腔和肺粘膜中强烈的 IgA 反应。因此，对常见皮肤定植者的免疫涉及协调的 T 细胞和 B 细胞反应，后者可以作为一种新的局部疫苗接种形式针对病原体重定向。