Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the National Institute for Health Research (Nihr) Oxford Biomedical Research Centre, Oxford, UK.
Expert Rev Vaccines. 2021 Dec;20(12):1515-1538. doi: 10.1080/14760584.2021.1984889. Epub 2021 Oct 25.
The public health burden caused by pathogenic Gram-negative bacteria is increasingly prominent due to antimicrobial resistance. The surface carbohydrates are potential antigens for vaccines against Gram-negative bacteria. The enhanced immunogenicity of the O-specific polysaccharide (O-SP) moiety of LPS when coupled to a carrier protein may protect against bacterial pathogens. However, because of the toxic lipid A moiety and relatively high costs of O-SP isolation, LPS has not been a popular vaccine antigen until recently.
In this review, we discuss the rationales for developing LPS-based glycoconjugate vaccines, principles of glycoconjugate-induced immunity, and highlight the recent developments and challenges faced by LPS-based glycoconjugate vaccines.
Advances in LPS harvesting, LPS chemical synthesis, and newer carrier proteins in the past decade have propelled LPS-based glycoconjugate vaccines toward further development, through to clinical evaluation. The development of LPS-based glycoconjugates offers a new horizon for vaccine prevention of Gram-negative bacterial infection.
由于抗菌药物耐药性的出现，致病性革兰氏阴性菌导致的公共卫生负担日益加重。表面碳水化合物是针对革兰氏阴性菌疫苗的潜在抗原。当与载体蛋白偶联时，脂多糖（LPS）的 O 特异性多糖（O-SP）部分的免疫原性增强可能有助于预防细菌病原体。然而，由于脂多糖的毒性脂质 A 部分和 O-SP 分离的相对较高成本，直到最近 LPS 才成为一种受欢迎的疫苗抗原。
在这篇综述中，我们讨论了开发基于 LPS 的糖缀合物疫苗的基本原理、糖缀合物诱导免疫的原理，并重点介绍了基于 LPS 的糖缀合物疫苗的最新进展和面临的挑战。
在过去十年中，LPS 的收获、LPS 的化学合成以及新型载体蛋白方面的进展推动了基于 LPS 的糖缀合物疫苗的进一步发展，直至进入临床评估。基于 LPS 的糖缀合物的开发为革兰氏阴性菌感染的疫苗预防提供了新的前景。
