Poolman Jan T, Torres Victor J, Missiakas Dominique, Welten Suzanne P M, Fernandez Jeffrey, DuMont Ashley L, O'Keeffe Anna, Konstantinov Sergey R, Morrow Brian, Burghout Peter, Grijpstra Jan, van Beers Miranda M C, Anish Chakkumkal, Beurret Michel, Geurtsen Jeroen, Rood Pauline M L, Koeberling Oliver, Shi Miaomiao, van den Dobbelsteen Germie P J M
Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V Archimedesweg 4-6, Leiden, The Netherlands.
Department of Microbiology, New York University School of Medicine, Alexandria Center for Life Science, New York, NY, USA.
NPJ Vaccines. 2025 Apr 20;10(1):78. doi: 10.1038/s41541-025-01119-8.
Staphylococcus aureus is a major cause of bacterial infection-related deaths. Increasing antimicrobial resistance highlights the urgent need for effective preventative strategies. Antibody-mediated opsonophagocytosis, the key mechanism for protection against S. aureus, is disabled by critical virulence factors such as Staphylococcal protein A (SpA) and leukocidin AB (LukAB). In our study, we combined genetically detoxified vaccine candidates SpA* and LukAB RARPR-33 with a T1 adjuvant aiming to restore host antibody functionality. To evaluate these vaccine candidates, we developed both surgical site infection (SSI) and superficial wound infection (SWI) models in minipigs. Our results showed a significant reduction in bacterial load and systemic dissemination in the SSI model, while skin infection severity was markedly decreased after intradermal immunization in the SWI model. This study introduces a novel S. aureus vaccine strategy by targeting immune evasion factors SpA and LukAB, utilizing potent T1 adjuvants, and employing minipig challenge models.
金黄色葡萄球菌是细菌感染相关死亡的主要原因。抗菌耐药性的增加凸显了对有效预防策略的迫切需求。抗体介导的调理吞噬作用是抵御金黄色葡萄球菌的关键机制，但被诸如葡萄球菌蛋白A（SpA）和杀白细胞素AB（LukAB）等关键毒力因子所破坏。在我们的研究中，我们将基因解毒的候选疫苗SpA*和LukAB RARPR-33与一种T1佐剂相结合，旨在恢复宿主抗体功能。为了评估这些候选疫苗，我们在小型猪中建立了手术部位感染（SSI）和浅表伤口感染（SWI）模型。我们的结果显示，在SSI模型中细菌载量和全身播散显著降低，而在SWI模型中，皮内免疫后皮肤感染严重程度明显降低。本研究通过靶向免疫逃逸因子SpA和LukAB、利用强效T1佐剂以及采用小型猪攻毒模型，引入了一种新型的金黄色葡萄球菌疫苗策略。
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