Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

IF 2.7 Q3 IMMUNOLOGY

Vaccine: X Pub Date : 2025-06-11 DOI:10.1016/j.jvacx.2025.100676

Sowmya Ajay Castro , Sarah Thomson , Helen Alexandra Shaw , Azul Zorzoli , Benjamin H. Meyer , Mark Reglinski , Mark McNeil , Helge C. Dorfmueller

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Abstract

Group A Streptococcus (Strep A) cause a wide range of human-exclusive infections, annually killing more than 500,000 people. Antibiotic resistance incidence of invasive Strep A tripled in the past decade and emphasises the need to develop a universal Strep A vaccine. In this study, we developed recombinant rhamnose polysaccharides (RhaPS), a validated universal Strep A vaccine candidate, presented on E. coli outer membrane vesicles (OMVs). We investigated OMV-RhaPS for their immunogenicity in the mouse and rabbit models. Through flow cytometry, ELISA, and immunofluorescence microscopy, we demonstrated that RhaPS-specific antibodies recognise Strep A strains via the Group A Carbohydrate (GAC) in S. pyogenes and the newly emerged S. dysgalactiae subsp. equisimilis. Elevated IL-17A levels from RhaPS-OMV-immunised splenocytes were detected when re-stimulated with the immunogen RhaPS-OMV. We report the efficacy and potency of recombinant produced RhaPS triggering antibodies that recognise Strep A bacteria and facilitate monocyte dependent opsonophagocytosis of several Strep A serotypes.

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鼠李糖多糖修饰的外膜囊泡作为一种针对化脓性链球菌和乳糖不良链球菌a群链球菌的候选疫苗。equisimilis

A组链球菌（Strep A）引起广泛的人类专属感染，每年造成50多万人死亡。在过去十年中，侵袭性甲型链球菌的抗生素耐药性发生率增加了两倍，这强调了开发一种通用甲型链球菌疫苗的必要性。在这项研究中，我们开发了重组鼠李糖多糖（RhaPS），这是一种经过验证的通用甲型链球菌候选疫苗，用于大肠杆菌外膜囊泡（OMVs）。我们研究了OMV-RhaPS在小鼠和家兔模型中的免疫原性。通过流式细胞术、ELISA和免疫荧光显微镜，我们证明了rhaps特异性抗体通过化脓性链球菌和新出现的dysgalactiae亚型中的A族碳水化合物（GAC）识别链球菌A菌株。equisimilis。用免疫原RhaPS-OMV再次刺激后，检测到经RhaPS-OMV免疫的脾细胞IL-17A水平升高。我们报道了重组生产的RhaPS的功效和效力，这些RhaPS触发了识别链球菌A细菌的抗体，并促进了几种链球菌A血清型的单核细胞依赖性调理吞噬。

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