DataSheet1_Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection.PDF

Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts older adults aged ≥65 years. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2–3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (18–22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.

尽管已可获得授权疫苗，但由肺炎链球菌（Streptococcus pneumoniae，以下简称肺炎球菌）引起的肺炎球菌病在全球范围内仍构成严重的传染病威胁。该疾病的临床表现包括肺炎、菌血症和脑膜炎，每年导致超过百万例死亡。肺炎球菌病对65岁及以上老年人影响尤为显著。由于疾病进展复杂且存在100种不同的细菌荚膜多糖血清型，干预措施变得复杂。这给开发针对肺炎球菌的广谱疫苗带来了挑战，目前疫苗主要利用荚膜多糖作为主要抗原成分。然而，现有的疫苗在保护老年人方面效果显著降低。我们先前开发了一种基于多糖脂质体包裹（Liposomal Encapsulation of Polysaccharides，简称LEPS）的疫苗平台，该平台针对现有肺炎球菌疫苗的局限性而设计，允许多糖和蛋白质抗原成分的非共价偶联，并在小鼠模型中保护幼鼠免受肺炎球菌感染。在本研究中，我们对配方进行了修改，使其更具经济性，并在老年宿主中测试了新型的LEPS疫苗。我们发现，在幼鼠（2-3个月大）中，LEPS引发的免疫反应与肺炎球菌结合疫苗Prevnar-13相当。此外，对老年小鼠（18-22个月大）的LEPS免疫接种诱导了与Prevnar-13相当的抗体水平和改善的抗体功能。重要的是，LEPS能够保护老年小鼠免受侵袭性和肺部局部肺炎球菌感染的侵害。总之，LEPS是一种替代且有效的疫苗策略，能够保护老年宿主免受肺炎球菌病不同表现形式的侵袭。