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亚单位疫苗:最新进展与挑战。

subunit vaccines: recent progress and challenges.

机构信息

School of Science, Monash University Malaysia, Bandar Sunway, Malaysia.

Tropical Medicine and Biology Multidisciplinary Platform, Monash University Malaysia, Bandar Sunway, Malaysia.

出版信息

Crit Rev Microbiol. 2024 Aug;50(4):434-449. doi: 10.1080/1040841X.2023.2215303. Epub 2023 May 21.

Abstract

is a Gram-negative, opportunistic pathogen that causes nosocomial infection with a high mortality rate in immunocompromised individuals. With the frequent emergence of multidrug-resistant strains that have rapidly gained resistance to most antibiotics, an extensive search for an effective vaccine is ongoing. Over the decade, many subunit vaccine candidates were identified using reverse vaccinology and animal studies for validation. Nineteen subunit vaccine candidates with a wide range of efficacy, from 14% to 100% preclinical survival rates, were included in this review. This article provides an updated review of several outer membrane proteins (Omp) that emerged as vaccine candidates with great potential, including OmpA, Omp34, Omp22 and BamA, based on their high conservancy, antigenicity, and immune protection against infection. However, there is still no licenced vaccine currently due to several practical issues that have yet to be resolved, such as inconsistencies between validation studies, antigen variability and insolubility. Moving forward, much investigation and innovation are still required to tackle these challenges for the regulatory approval of an subunit vaccine, including standardisation of immunisation study parameters, improving antigen solubility and the incorporation of nucleic acid vaccine technology.

摘要

是一种革兰氏阴性、机会性病原体,在免疫功能低下的个体中会引起医院获得性感染,死亡率很高。由于频繁出现对大多数抗生素迅速产生耐药性的多药耐药菌株,正在广泛寻找有效的疫苗。在过去十年中,已经使用反向疫苗学和动物研究鉴定了许多亚单位疫苗候选物进行验证。本综述纳入了 19 种亚单位疫苗候选物,其临床前生存率从 14%到 100%不等,具有广泛的疗效。本文基于其高度保守性、抗原性和对感染的免疫保护作用,综述了几种作为疫苗候选物的外膜蛋白 (Omp),包括 OmpA、Omp34、Omp22 和 BamA,这些候选物具有很大的潜力。然而,由于尚未解决的几个实际问题,如验证研究的不一致性、抗原变异性和不溶性,目前仍没有许可的疫苗。为了获得监管部门对亚单位疫苗的批准,需要进行大量的研究和创新来应对这些挑战,包括免疫研究参数的标准化、提高抗原溶解度以及核酸疫苗技术的应用。

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