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Evaluation of inactivated Bordetella pertussis as a delivery system for the immunization of mice with Pneumococcal Surface Antigen A.
PLOS ONE ( IF 2.9 ) Pub Date : 2020-01-16 , DOI: 10.1371/journal.pone.0228055
Julia T Castro 1 , Giuliana S Oliveira 1 , Melissa A Nishigasako 1 , Anne-Sophie Debrie 2 , Eliane N Miyaji 1 , Alessandra Soares-Schanoski 1 , Milena A Akamatsu 3 , Camille Locht 2 , Paulo L Ho 3 , Nathalie Mielcarek 2 , Maria Leonor S Oliveira 1
Affiliation  

Pneumococcal Surface Protein A (PspA) has been successfully tested as vaccine candidate against Streptococcus pneumoniae infections. Vaccines able to induce PspA-specific antibodies and Th1 cytokines usually provide protection in mice. We have shown that the whole cell pertussis vaccine (wP) or components from acellular pertussis vaccines, such as Pertussis Toxin or Filamentous Hemagglutinin (FHA), are good adjuvants to PspA, suggesting that combined pertussis-PspA vaccines would be interesting strategies against the two infections. Here, we evaluated the potential of wP as a delivery vector to PspA. Bordetella pertussis strains producing a PspA from clade 4 (PspA4Pro) fused to the N-terminal region of FHA (Fha44) were constructed and inactivated with formaldehyde for the production of wPPspA4Pro. Subcutaneous immunization of mice with wPPspA4Pro induced low levels of anti-PspA4 IgG, even after 3 doses, and did not protect against a lethal pneumococcal challenge. Prime-boost strategies using wPPspA4Pro and PspA4Pro showed that there was no advantage in using the wPPspA4Pro vaccine. Immunization of mice with purified PspA4Pro induced higher levels of antibodies and protection against pneumococcal infection than the prime-boost strategies. Finally, purified Fha44:PspA4Pro induced high levels of anti-PspA4Pro IgG, but no protection, suggesting that the antibodies induced by the fusion protein were not directed to protective epitopes.

中文翻译:

评估灭活的百日咳博德特氏菌作为用肺炎球菌表面抗原A免疫小鼠的递送系统。

肺炎球菌表面蛋白A(PspA)已成功测试为抗肺炎链球菌感染的候选疫苗。能够诱导PspA特异性抗体和Th1细胞因子的疫苗通常在小鼠中提供保护。我们已经表明,全细胞百日咳疫苗(wP)或无细胞百日咳疫苗的成分,例如百日咳毒素或丝状血凝素(FHA),都是PspA的良好佐剂,这表明结合百日咳-PspA疫苗是针对这两种疫苗的有趣策略感染。在这里,我们评估了wP作为PspA传递载体的潜力。构建了从进化枝4(PspA4Pro)融合到FHA N端区域(Fha44)产生PspA的百日咳博德特氏菌菌株,并用甲醛使其灭活,从而生产wPPspA4Pro。用wPPspA4Pro进行的小鼠皮下免疫即使3剂后也能产生低水平的抗PspA4 IgG,并且不能抵抗致命的肺炎球菌攻击。使用wPPspA4Pro和PspA4Pro的初免-加强策略显示,使用wPPspA4Pro疫苗没有优势。与初免-加强策略相比,用纯化的PspA4Pro免疫小鼠可诱导更高水平的抗体和抗肺炎球菌感染。最后,纯化的Fha44:PspA4Pro诱导了高水平的抗PspA4Pro IgG,但没有保护作用,表明融合蛋白诱导的抗体没有针对保护性表位。使用wPPspA4Pro和PspA4Pro的初免-加强策略显示,使用wPPspA4Pro疫苗没有优势。与初免-加强策略相比,用纯化的PspA4Pro免疫小鼠可诱导更高水平的抗体和抗肺炎球菌感染。最后,纯化的Fha44:PspA4Pro诱导了高水平的抗PspA4Pro IgG,但没有保护作用,表明融合蛋白诱导的抗体没有针对保护性表位。使用wPPspA4Pro和PspA4Pro的初免-加强策略显示,使用wPPspA4Pro疫苗没有优势。与初免-加强策略相比,用纯化的PspA4Pro免疫小鼠可诱导更高水平的抗体和抗肺炎球菌感染。最后,纯化的Fha44:PspA4Pro诱导了高水平的抗PspA4Pro IgG,但没有保护作用,表明融合蛋白诱导的抗体没有针对保护性表位。
更新日期:2020-01-17
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