Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
J Infect Dis. 2019 Jan 7;219(2):323-334. doi: 10.1093/infdis/jiy506.
Protection against encapsulated bacteria can be elicited using polysaccharide vaccines. These antigens often behave as T-cell-independent type 2 antigens (TI-2 Ags). However, TI-2 Ags, including pneumococcal polysaccharides, often elicit weak immunoglobulin G (IgG) responses and are refractive to boosting. Conjugate vaccines have not completely overcome this challenge and hence, alternative strategies are required to enhance polysaccharide vaccine responses. Herein, we describe an adjuvant consisting of a Toll-like receptor and C-type lectin receptor agonist pairing that significantly increases primary immunoglobulin M and IgG responses to TI-2 Ags as well as enables significant boosting when coadministered with polysaccharide vaccines. Consistent with this, the adjuvant significantly increased the generation of both TI-2 memory B cells and long-lived antibody secreting cells. Adjuvant effects were highly dependent on B-cell-intrinsic MyD88, but not Trif expression. Importantly, coadministration of the adjuvant with the Pneumovax vaccine significantly increased the protective efficacy of vaccination in a lethal challenge mouse model of pneumococcal respiratory infection. Collectively, these data provide evidence that B-cell-directed adjuvants have promise in significantly improving the quality and quantity of serologic and B-cell memory responses to clinically relevant polysaccharide vaccines.
针对囊膜细菌的保护作用可以通过多糖疫苗来诱导。这些抗原通常表现为 T 细胞非依赖性 2 型抗原(TI-2 抗原)。然而,包括肺炎球菌多糖在内的 TI-2 抗原通常会引起较弱的免疫球蛋白 G(IgG)反应,并且对增强反应具有抵抗力。结合疫苗并未完全克服这一挑战,因此需要采用替代策略来增强多糖疫苗的反应。在此,我们描述了一种佐剂,由 Toll 样受体和 C 型凝集素受体激动剂配对组成,该佐剂可显著提高 TI-2 抗原的初次免疫球蛋白 M 和 IgG 反应,并在与多糖疫苗共同给药时实现显著增强。与之一致的是,该佐剂显著增加了 TI-2 记忆 B 细胞和长寿抗体分泌细胞的产生。佐剂作用高度依赖于 B 细胞内在的 MyD88,但不依赖于 Trif 表达。重要的是,佐剂与 Pneumovax 疫苗共同给药可显著提高肺炎球菌呼吸道感染致死性挑战小鼠模型中疫苗接种的保护效力。总之,这些数据提供了证据,表明针对 B 细胞的佐剂有望显著提高临床相关多糖疫苗的血清学和 B 细胞记忆反应的质量和数量。