Discovery and engineering of the antibody response against a prominent skin commensal.
Discovery and engineering of the antibody response against a prominent skin commensal.
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针对突出皮肤共生体的抗体反应的发现和工程设计。
DOI：
10.1101/2024.01.23.576900
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Pham,ThiPhuongTha
中科院分区：
文献类型：
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作者：
Bousbaine,Djenet;Bauman,KatherineD;Chen,YErin;Yu,VictorK;Lalgudi,PranavV;Naziripour,Arash;Veinbachs,Alessandra;Phung,JennieL;Nguyen,TamTD;Swenson,JoyceM;Lee,YueE;Dimas,Alex;Jain,Sunit;Meng,Xiandong;Pham,ThiPhuongTha
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产生CD 8 +T细胞反应。然而，这种抗肿瘤免疫程序的范围和目的并没有很好地定义，限制了我们在治疗上利用它的能力。在这里，我们表明，这种殖民者也诱导了一种有效的，持久的，特异性的抗体反应，这是在人类和非人类灵长类动物中保守的。一系列的S。epidermidiscell-wall突变体揭示了细胞表面蛋白Aap是一个主要的目标。通过在小鼠体内定植一株S.通过使用其中Aap的平行β-螺旋结构域被破伤风毒素片段C取代的表皮毒素，我们引发了保护小鼠免受致死性攻击的有效中和抗体应答。S.表皮去表达Aap-SpyCatcher嵌合体可以与重组免疫原缀合;所得的标记的唾液酸在生理定殖条件下产生高滴度的抗体，包括鼻粘膜中的稳健伊加应答。因此，对普通皮肤定植者的免疫涉及协调的T和B细胞应答，后者可以作为局部疫苗接种的新形式针对病原体重定向。
The ubiquitous skin colonistStaphylococcus epidermidiselicits a CD8+T cell response pre-emptively, in the absence of an infection. 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 ofS. epidermidiscell-wall mutants revealed that the cell surface protein Aap is a predominant target. By colonizing mice with a strain ofS. epidermidisin 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 ofS. epidermidisexpressing an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits high titers of antibody under conditions of physiologic colonization, including a robust IgA response in the nasal 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.