Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu, Sichuan Province 610041, China.
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu, Sichuan Province 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, No. 17, Section 3, South Renmin Road, Chengdu, Sichuan Province 610041, China.
Vaccine. 2019 Jan 29;37(5):721-731. doi: 10.1016/j.vaccine.2018.12.021. Epub 2019 Jan 2.
Few children living in southwest China are vaccinated against Streptococcus pneumoniae (S. pneumoniae), which is an important pathogen in causing high morbidity and high mortality. This study aimed the molecular characterization of S. pneumoniae strains isolated from children and a new vaccine strategy based on a potential protein antigen.
Molecular characterizations, including serotype, virulence gene and pilus analyses, were performed using PCR. Seven housekeeping genes were sequenced to identify the sequence types (STs), and antibiotic resistance was analysed using the microdilution broth method. In addition, we evaluated the protective effects of recombinant plasmin- and fibronectin-binding protein A (rPfbA) in murine pneumococcal infection models by challenge and passive transfer analyses, and assessed cytokine changes after immunization.
The prevalent serotypes were 19F (31.4%), 19A (21.6%), 6B (13.7%), 14 (11.8%) and 23F (9.8%), and the coverage rates of the 13-valent pneumococcal conjugate vaccine (PCV13) were high in 93.3% of the isolates. The predominant STs were ST271 (23.5%), ST320 (21.6%) and ST876 (11.8%). Most of the S. pneumoniae isolates were resistant to erythromycin (95.1%) and clindamycin (90.2%). The molecular distributions and antibiotic resistance rates of the S. pneumoniae isolates differed between the plateau and the basin regions. More than 93% of the S. pneumoniae isolates carried ply, cbpA, phtD and nanA, and over half of the isolates carried pilus-1, pilus-2 and pfbA. Mucosal immunization with rPfbA induced pneumococcal specific antibody responses which provided to eliminate colonization in lung and nasopharynx, and protection against pneumococcal challenge.
Vaccine strategies based on epidemiological surveillance can be more adaptive to specific areas, reduce costs and protect against changing antigenic sites. We advise that children currently living in southwest China be vaccinated with PCV13.
中国西南部很少有儿童接种肺炎链球菌 (S. pneumoniae) 疫苗,而肺炎链球菌是导致高发病率和高死亡率的重要病原体。本研究旨在对从儿童中分离出的肺炎链球菌菌株进行分子特征分析,并提出基于潜在蛋白抗原的新型疫苗策略。
采用 PCR 法进行血清型、毒力基因和菌毛分析等分子特征分析。对 7 个管家基因进行测序以确定序列类型 (ST),并采用微量稀释肉汤法分析抗生素耐药性。此外,我们通过攻毒和被动转移分析评估了重组纤溶酶和纤维结合蛋白 A (rPfbA) 在小鼠肺炎球菌感染模型中的保护作用,并检测了免疫后的细胞因子变化。
流行的血清型为 19F (31.4%)、19A (21.6%)、6B (13.7%)、14 (11.8%) 和 23F (9.8%),93.3%的分离株对 13 价肺炎球菌结合疫苗 (PCV13) 的覆盖率较高。主要 ST 型为 ST271 (23.5%)、ST320 (21.6%) 和 ST876 (11.8%)。大多数肺炎链球菌分离株对红霉素 (95.1%) 和克林霉素 (90.2%) 耐药。高原和盆地地区肺炎链球菌的分子分布和抗生素耐药率不同。超过 93%的肺炎链球菌分离株携带 ply、cbpA、phtD 和 nanA,超过一半的分离株携带 pilus-1、pilus-2 和 pfbA。rPfbA 黏膜免疫可诱导肺炎球菌特异性抗体反应,从而消除肺部和鼻咽部的定植,并提供针对肺炎球菌攻毒的保护。
基于流行病学监测的疫苗策略可以更好地适应特定地区,降低成本,并预防抗原性变化。我们建议目前生活在中国西南部的儿童接种 PCV13。