National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, PR China.
Department of Clinical Hematology, College of Pharmacy, Army Medical University, Chongqing 400038, PR China.
Vaccine. 2024 Oct 3;42(23):126217. doi: 10.1016/j.vaccine.2024.126217. Epub 2024 Aug 19.
Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen and the major cause of healthcare-associated infections, which are increasingly complicated by the prevalence of highly invasive and hyper-virulent K. pneumoniae strains, necessitating the development of alternative strategies for combatting infections caused by this bacterium. In this study, we successfully constructed a fusion antigen called KP-Ag1, comprising three antigens (GlnH, FimA, and KPN_00466) that were previously identified through reverse vaccinology. Immunization with KP-Ag1 formulated with Al(OH) adjuvant elicited robust humoral and cellular immune response in mice, and conferred protective immunity in a murine model of K. pneumoniae lung infection. Further analysis of serum IgG subtypes from mice immunized with KP-Ag1 revealed a predominant IgG1 response, indicating that KP-Ag1 predominantly induces a Th2-biased immune response. Additionally, opsonophagocytic killing assay suggested that humoral immune responses play a pivotal role in mediating protection conferred by KP-Ag1. Moreover, KP-Ag1 was found to promote the activation and maturation of BMDCs in vitro, which is essential for subsequent efficient antigen presentation. More importantly, vaccination with KP-Ag1 demonstrated cross-protective efficacy against clinical isolates of K. pneumoniae varying in serotypes, antibiotic resistance, and virulence profiles. Therefore, KP-Ag1 holds promise as a candidate for K. pneumoniae vaccine development.
肺炎克雷伯菌（Klebsiella pneumoniae，K. pneumoniae）是一种机会致病菌，也是导致医疗保健相关感染的主要原因。由于高侵袭性和高毒性肺炎克雷伯菌菌株的流行，这些感染变得日益复杂，因此需要开发替代策略来对抗这种细菌引起的感染。在本研究中，我们成功构建了一种融合抗原，称为 KP-Ag1，它由通过反向疫苗学方法鉴定的三种抗原（GlnH、FimA 和 KPN_00466）组成。用 Al(OH)佐剂配制的 KP-Ag1 免疫可在小鼠中引起强烈的体液和细胞免疫应答，并在肺炎克雷伯菌肺部感染的小鼠模型中提供保护免疫力。进一步分析用 KP-Ag1 免疫的小鼠血清 IgG 亚型表明存在主要的 IgG1 反应，表明 KP-Ag1 主要诱导 Th2 偏向的免疫应答。此外，调理吞噬杀伤测定表明，体液免疫应答在介导 KP-Ag1 提供的保护中起关键作用。此外，KP-Ag1 被发现可在体外促进 BMDCs 的激活和成熟，这对于随后有效的抗原呈递至关重要。更重要的是，KP-Ag1 疫苗接种对不同血清型、抗生素耐药性和毒力谱的临床分离株的肺炎克雷伯菌具有交叉保护效力。因此，KP-Ag1 有望成为肺炎克雷伯菌疫苗开发的候选物。
