Several vaccines targeting bacterial pathogens show reduced efficacy upon concurrent viral infection, indicating that a new vaccinology approach is required. To identify antigens for the human pathogen that are effective following influenza infection, we performed CRISPRi-seq in a murine model of superinfection and identified the conserved gene as crucial for virulence. We show that LafB is a membrane-associated, intracellular protein that catalyzes the formation of galactosyl-glucosyl-diacylglycerol, a glycolipid important for cell wall homeostasis. Respiratory vaccination with recombinant LafB, in contrast to subcutaneous vaccination, was highly protective against serotypes 2, 15A, and 24F in a murine model. In contrast to standard capsule-based vaccines, protection did not require LafB-specific antibodies but was dependent on airway CD4 T helper 17 cells. Healthy human individuals can elicit LafB-specific immune responses, indicating LafB antigenicity in humans. Collectively, these findings present a universal pneumococcal vaccine antigen that remains effective following influenza infection.

中文翻译：

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保守抗原诱导呼吸道 Th17 介导的针对肺炎球菌二重感染的广泛血清型保护

几种针对细菌病原体的疫苗在并发病毒感染时显示出功效降低，这表明需要一种新的疫苗学方法。为了鉴定在流感感染后有效的人类病原体抗原，我们在小鼠重复感染模型中进行了 CRISPRi-seq，并鉴定了对毒力至关重要的保守基因。我们发现 LafB 是一种膜相关的细胞内蛋白，可催化半乳糖基-葡萄糖基-二酰基甘油的形成，半乳糖基-葡萄糖基-二酰基甘油是一种对细胞壁稳态很重要的糖脂。与皮下接种相比，重组 LafB 呼吸道疫苗接种在小鼠模型中对血清型 2、15A 和 24F 具有高度保护作用。与标准胶囊疫苗相比，保护不需要 LafB 特异性抗体，而是依赖于气道 CD4 T 辅助 17 细胞。健康的人类个体可以引发 LafB 特异性免疫反应，表明 LafB 在人类中具有抗原性。总的来说，这些发现提出了一种通用肺炎球菌疫苗抗原，在流感感染后仍然有效。