Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, WV, United States.
Vaccine Development Center at West Virginia University Health Sciences Center, Morgantown, WV, United States.
Front Immunol. 2019 Oct 23;10:2497. doi: 10.3389/fimmu.2019.02497. eCollection 2019.
is an opportunistic pathogen causing acute and chronic respiratory infections associated with morbidity and mortality, especially in patients with cystic fibrosis. Vaccination against before colonization may be a solution against these infections and improve the quality of life of at-risk patients. To develop a vaccine against , we formulated a novel peptide-based subunit vaccine based on the extracellular regions of one of its major siderophore receptors, FpvA. We evaluated the effectiveness and immunogenicity of the FpvA peptides conjugated to keyhole limpet hemocyanin (KLH) with the adjuvant curdlan in a murine vaccination and challenge model. Immunization with the FpvA-KLH vaccine decreased the bacterial burden and lung edema after challenge. Vaccination with FpvA-KLH lead to antigen-specific IgG and IgM antibodies in sera, and IgA antibodies in lung supernatant. FpvA-KLH immunized mice had an increase in recruitment of CD11b dendritic cells as well as resident memory CD4 T cells in the lungs compared to non-vaccinated challenged mice. Splenocytes isolated from vaccinated animals showed that the FpvA-KLH vaccine with the adjuvant curdlan induces antigen-specific IL-17 production and leads to a Th17 type of immune response. These results indicate that the intranasal FpvA-KLH conjugate vaccine can elicit both mucosal and systemic immune responses. These observations suggest that the intranasal peptide-based FpvA-KLH conjugate vaccine with curdlan is a potential vaccine candidate against pneumonia.
是一种机会性病原体,可引起急性和慢性呼吸道感染,与发病率和死亡率有关,特别是在囊性纤维化患者中。在定植前接种针对 的疫苗可能是预防这些感染的一种方法,并可提高高危患者的生活质量。为了开发针对 的疫苗,我们基于其主要铁载体受体之一 FpvA 的细胞外区域,设计了一种新型基于肽的 亚单位疫苗。我们在小鼠疫苗接种和挑战模型中,用佐剂角叉菜胶评估了与匙孔血蓝蛋白(KLH)偶联的 FpvA 肽的有效性和免疫原性。用 FpvA-KLH 疫苗免疫可降低 挑战后的细菌负荷和肺水肿。FpvA-KLH 疫苗接种可导致血清中产生针对抗原的 IgG 和 IgM 抗体,以及肺上清液中的 IgA 抗体。与未接种挑战的对照小鼠相比,FpvA-KLH 免疫的小鼠肺部 CD11b 树突状细胞和固有记忆性 CD4 T 细胞的募集增加。从接种动物分离的脾细胞表明,用角叉菜胶佐剂的 FpvA-KLH 疫苗可诱导针对抗原的 IL-17 产生,并导致 Th17 型免疫反应。这些结果表明,鼻内 FpvA-KLH 缀合物疫苗可引发黏膜和全身免疫反应。这些观察结果表明,用角叉菜胶的鼻内肽基 FpvA-KLH 缀合物疫苗是针对 肺炎的潜在疫苗候选物。