当前位置 :首页>研究报道

中国西南地区儿童肺炎链球菌的分子特征及潜在蛋白疫苗rPfbA的评估

发布者:抗性基因网 时间:2019-01-08 浏览量:580

背景:
生活在中国西南地区的儿童很少接种肺炎链球菌(肺炎链球菌)疫苗,肺炎链球菌是导致高发病率和高死亡率的重要病原体。本研究旨在分析儿童肺炎链球菌菌株的分子特征,以及基于潜在蛋白质抗原的新疫苗策略。

方法:
使用PCR进行分子表征,包括血清型,毒力基因和菌毛分析。对7个管家基因进行测序以鉴定序列类型(ST),并使用微量稀释肉汤法分析抗生素抗性。此外,我们通过攻击和被动转移分析评估了重组纤溶酶和纤连蛋白结合蛋白A(rPfbA)在小鼠肺炎球菌感染模型中的保护作用,并评估了免疫后细胞因子的变化。

结果:
流行的血清型分别为19F(31.4%),19A(21.6%),6B(13.7%),14(11.8%)和23F(9.8%),13价肺炎球菌结合疫苗(PCV13)的覆盖率为93.3%的分离株高。主要的STs是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%)具有抗性。肺炎链球菌分离株的分子分布和抗生素耐药率在高原和盆地区域之间不同。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菌毛-1,菌毛-2和pfbA。用rPfbA进行的粘膜免疫诱导肺炎球菌特异性抗体应答,其提供消除肺和鼻咽中的定植,以及防止肺炎球菌攻击。

结论:
基于流行病学监测的疫苗策略可以更适应特定区域,降低成本并防止变化的抗原位点。我们建议目前居住在中国西南地区的儿童接种PCV13疫苗。


BACKGROUND:
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.

METHODS:
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.

RESULTS:
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.

CONCLUSION:
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.

https://www.ncbi.nlm.nih.gov/pubmed/30611601