Identification of protective pneumococcal antigens from a surface protein library

描述（由申请人提供）：抗肺炎链球菌的结合疫苗（与载体蛋白结合的荚膜多糖）是可用的，但受疫苗中包括的血清型的限制；此外，在许多引进结合疫苗的国家也观察到血清型替代。因此，提供特定物种保护的替代疫苗将是一项重要的公共卫生进展。两种类型的获得性免疫，TH17细胞介导和抗体介导，已被证明分别提供对鼻咽定植和侵袭性疾病的保护。细菌表面的蛋白质是疫苗开发的有吸引力的靶标，因为它们对抗体的可及性和促进调理吞噬的可能性。我们将开发一个肺炎球菌物种保守的表面蛋白文库，并筛选候选疫苗，提供TH17依赖的抗定植保护和抗体介导的抗肺炎球菌疾病保护。TH17刺激蛋白的筛选将首先在小鼠模型中进行，然后激发IL-17A

DESCRIPTION (provided by applicant): Conjugate vaccines (capsular polysaccharides conjugated to carrier proteins) against Streptococcus pneumoniae are available but are limited by the serotypes included in the vaccines; furthermore serotype replacement had been observed in many countries that have introduced conjugate vaccines. Therefore, alternative vaccines that provide species-specific protection would represent an important public health advance. Two types of acquired immunity, TH17 cells- and antibody-mediated, have been shown to provide protection against nasopharyngeal colonization and invasive disease, respectively. Proteins on the bacterial surface represent attractive targets for vaccine development due to their accessibility to antibodies and the possibility of promoting opsonophagocytosis. We will develop a pneumococcal species-conserved surface protein library and screen it for vaccine candidates that provide TH17 dependent protection against colonization and antibody-mediated protection against pneumococcal disease. Screens for TH17 stimulatory proteins will be carried out first in mouse models for elicitation of IL-17A after pneumococcal exposure; these results will then be confirmed by examination of the TH17 response from adenoidal cells obtained from children. Antigens that elicit these responses in both mice and pediatric adenoidal cells will then be tested for protection against colonization and disease in murine models. Successful completion of this will both advance the field of pneumococcal vaccine research and provide a proof-of-concept strategy for antigen discovery for other pathogens, such as Staphylococcus aureus and group A streptococcus, in which both T and B cell immunity play important and complementary roles.