MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK.
Microb Biotechnol. 2024 Mar;17(3):e14446. doi: 10.1111/1751-7915.14446.
Developing protein-based vaccines against bacteria has proved much more challenging than producing similar immunisations against viruses. Currently, anti-bacterial vaccines are designed using methods based on reverse vaccinology. These identify broadly conserved, immunogenic proteins using a combination of genomic and high-throughput laboratory data. While this approach has successfully generated multiple rationally designed formulations that show promising immunogenicity in animal models, few have been licensed. The difficulty of inducing protective immunity in humans with such vaccines mirrors the ability of many bacteria to recolonise individuals despite recognition by natural polyvalent antibody repertoires. As bacteria express too many antigens to evade all adaptive immune responses through mutation, they must instead inhibit the efficacy of such host defences through expressing surface structures that interface with the immune system. Therefore, 'immune interface interference' (I3) vaccines that target these features should synergistically directly target bacteria and prevent them from inhibiting responses to other surface antigens. This approach may help us understand the efficacy of the two recently introduced immunisations against serotype B meningococci, which both target the Factor H-binding protein (fHbp) that inhibits complement deposition on the bacterial surface. Therefore, I3 vaccine designs may help overcome the current challenges of developing protein-based vaccines to prevent bacterial infections.
开发针对细菌的蛋白质疫苗比生产针对病毒的类似疫苗要困难得多。目前，抗细菌疫苗是使用基于反向疫苗学的方法设计的。这些方法使用基因组和高通量实验室数据的组合来识别广泛保守、具有免疫原性的蛋白质。虽然这种方法已经成功地产生了多种合理设计的配方，这些配方在动物模型中显示出有希望的免疫原性，但很少有获得许可。这种疫苗在人类中诱导保护性免疫的困难反映了许多细菌即使被天然多价抗体库识别，也有能力重新定植个体。由于细菌表达的抗原太多，无法通过突变逃避所有适应性免疫反应，因此它们必须通过表达与免疫系统相互作用的表面结构来抑制这种宿主防御的效果。因此，针对这些特征的“免疫界面干扰”（I3）疫苗应该能够协同地直接靶向细菌，并防止它们抑制对其他表面抗原的反应。这种方法可能有助于我们了解最近推出的两种针对 B 型脑膜炎球菌的免疫接种的效果，这两种免疫接种都针对抑制补体在细菌表面沉积的因子 H 结合蛋白（fHbp）。因此，I3 疫苗设计可能有助于克服开发用于预防细菌感染的基于蛋白质疫苗的当前挑战。
