Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4⁺ T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4⁺ T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10Rα on CD4⁺ T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-γ responses. We thus propose that IL-10 secreting, SA-experienced CD4⁺ T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development.

致病菌已经进化出许多与宿主共存的策略，但免疫逃避机制如何导致开发针对致病菌的疫苗的困难尚不清楚。与此同时，金黄色葡萄球菌 （SA） 迄今为止一直抵制人类疫苗的开发。在这里，我们表明先前的 SA 暴露会诱导非保护性 CD4 ⁺ T 细胞印记，导致保护性 IsdB 疫苗反应减弱。从机制上讲，这些经历过 SA 的 CD4⁺ T 细胞表达 IL-10，IL-10 通过疫苗接种进一步扩增，并通过与 CD4⁺ T 细胞上的 IL-10Rα 结合并抑制 IL-17A 产生来阻碍疫苗保护。IL-10 还介导 IsdB 和 sdrE 多抗原疫苗的交叉抑制。相比之下，SA IsdB、IsdA 和 MntC 疫苗的低效可以通过与促进 IL-17A 和 IFN-γ 反应的佐剂联合治疗来克服。因此，我们提出分泌 IL-10、SA 经历的 CD4 ⁺ T 细胞印记代表了一种葡萄球菌免疫逃逸机制，未来疫苗开发需要考虑该机制。