title: Mucosal and systemic immunization with a novel attenuated pneumococcal vaccine candidate confer serotype independent protection against Streptococcus pneumoniae in mice.
abstract: Despite the availability of effective vaccines, Streptococcus pneumoniae is still one of the major infectious diseases causing substantial morbidity and mortality in children under 5 years old. In this study, we demonstrate the protective efficacy of S. pneumoniae SPY1, a novel live attenuated vaccine strain against pneumococcal infection in murine models. This strain was characterized by defects in three important pneumococcal virulence factors including capsule, teichoic acids and pneumolysin. The lactate dehydrogenase assays and in vivo animal experiments demonstrated a significantly attenuated virulence and a reduced nasopharyngeal colonization for the SPY1 strain. We also show that mucosal and systemic immunization with the live SPY1 strain induced protective immune responses against pneumococci. Mucosal immunization with SPY1 offered better protection against colonization challenge with strains TIGR4 and serotype 19F than systemic SPY1 immunization. In invasive infection models, mucosal vaccination with the SPY1 strain conferred complete protection against D39 and clinical serotype 6B and 3 strains. Notably, intranasal vaccination with the SPY1 strain conferred superior protection against pneumococcal invasive disease compared with the commercial available vaccines. SPY1 strain was shown to elicit high levels of serotype-independent antibodies and a mixed cellular immune response. Besides, the SPY1 serum was able to passively protect mice against invasive challenge with D39 strain, indicating the protective effect of the antibody-mediated responses. Together, the SPY1 strain may be a promising live vaccine strain to protect pneumococcal infection.
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Transfusion, XiangYa Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Run
authors.initials: R
authors.lastname: Yao
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Pang
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: apoe@163.com.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: yibingyin56@126.com.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D058491:Bacterial Load; D056738:Cross Protection; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D065288:Serogroup; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D014613:Vaccines, Attenuated
keywords: Live attenuated vaccine; Mucosal immunization; Protection; Streptococcus pneumoniae