Traditional vaccines derived from attenuated or inactivated pathogens are effective at inducing antibody-based protective immune responses but tend to be highly reactogenic, causing notable adverse effects. Vaccines with superior safety profiles can be produced by subunit approaches, utilizing molecularly defined antigens (e.g., proteins and polysaccharides). These antigens, however, often elicit poor immunological responses, necessitating the use of adjuvants. Immunostimulatory adjuvants have the capacity to activate antigen presenting cells directly through specific receptors (e.g., Toll-like receptors (TLRs)), resulting in enhanced presentation of antigens as well as the secretion of proinflammatory chemokines and cytokines. Consequently, innate immune responses are amplified and adaptive immunity is generated. Recently, site-specific conjugation of such immunostimulatory adjuvants (e.g., TLR ligands) onto defined antigens has shown superior efficacy over unconjugated mixtures, suggesting that the development of chemically characterized immunostimulatory adjuvants and optimized approaches for their conjugation with antigens may provide a better opportunity for the development of potent, novel vaccines. This review briefly summarizes various TLR agonists utilized as immunostimulatory adjuvants and focuses on the development of techniques (e.g., recombinant, synthetic, and semisynthetic) for generating adjuvant–antigen fusion vaccines incorporating peptide or protein antigens.

中文翻译：

---

生产蛋白质或多肽抗原和共价连接的Toll样受体配体的亚单位疫苗的生物缀合方法

源自减毒或灭活病原体的传统疫苗可有效诱导基于抗体的保护性免疫反应，但往往具有很高的反应原性，从而引起明显的不良反应。具有优异安全性的疫苗可以通过亚基方法，利用分子确定的抗原（例如蛋白质和多糖）生产。但是，这些抗原通常引起较差的免疫反应，因此需要使用佐剂。免疫刺激佐剂具有直接通过特定受体（例如Toll样受体（TLR））激活抗原呈递细胞的能力，从而导致抗原呈递增加以及促炎性趋化因子和细胞因子的分泌。因此，先天免疫应答被放大并产生适应性免疫。最近，此类免疫刺激佐剂（例如TLR配体）在特定抗原上的位点特异性缀合已显示出优于未缀合混合物的功效，这表明化学表征的免疫刺激佐剂的开发以及其与抗原缀合的优化方法可能会为开发提供更好的机会强力，新颖的疫苗。这篇综述简要总结了各种用作免疫刺激佐剂的TLR激动剂，并着重于技术的发展（例如重组，合成和半合成），以产生结合了肽或蛋白质抗原的佐剂-抗原融合疫苗。这表明化学特征的免疫刺激佐剂的开发及其与抗原结合的优化方法可能为开发有效的新型疫苗提供更好的机会。这篇综述简要总结了各种用作免疫刺激佐剂的TLR激动剂，并着重于技术的发展（例如重组，合成和半合成），以产生结合了肽或蛋白质抗原的佐剂-抗原融合疫苗。这表明化学特征的免疫刺激佐剂的开发及其与抗原结合的优化方法可能为开发有效的新型疫苗提供更好的机会。这篇综述简要总结了各种用作免疫刺激佐剂的TLR激动剂，并着重于技术的发展（例如重组，合成和半合成），以产生结合了肽或蛋白质抗原的佐剂-抗原融合疫苗。