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新型肺炎球菌多糖疫苗与乙肝表面抗原偶联诱导小鼠整体免疫。

Elicitation of integrated immunity in mice by a novel pneumococcal polysaccharide vaccine conjugated with HBV surface antigen.

机构信息

Institute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, 650118, China.

Walvax Biotechnology Co., Ltd, Kunming, 650106, China.

出版信息

Sci Rep. 2020 Apr 14;10(1):6470. doi: 10.1038/s41598-020-62185-7.

Abstract

The conjugation of polysaccharides with an effective carrier protein is critical for the development of effective bacterial polysaccharide vaccines. Therefore, the identification and optimization of carrier proteins to induce an effective immune response is necessary for developing a combined vaccine. In the current study, we utilized hepatitis B virus surface antigen (HBsAg) as a novel carrier protein combined with a capsular polysaccharide molecule to develop a new pneumococcal conjugated vaccine. The specific antibodies and T cell immune response against the capsular polysaccharide and HBsAg in the mice immunized with this conjugated vaccine were evaluated. In addition, the unique gene profiles of immune cells induced by this conjugated vaccine in the immunized mice were analyzed. Our results demonstrated that the vaccine consisting of pneumonia type 33 F capsular polysaccharide (Pn33Fps) conjugated with HBsAg can induce strong specific immune responses against both antigens in vivo in immunized mice. Furthermore, the conjugated vaccine induced higher expression of genes related to the activation of immunity and higher antibody titers against Pn33Fps and HBsAg in mice than those obtained via vaccination with a single antigen. Analyses of the dynamic expression changes in immunity-related genes in mice immunized with Pn33Fps_HBs, Pn33Fps, or HBsAg indicated the potent immunogenicity of the conjugated vaccine. In addition, a pathological evaluation of the organs from immunized mice further suggested that the conjugated vaccine is safe. Together, these results indicate that a conjugated vaccine consisting of Pn33Fps with HBsAg is a novel and effective vaccine.

摘要

多糖与有效载体蛋白的结合对于开发有效的细菌性多糖疫苗至关重要。因此,鉴定和优化载体蛋白以诱导有效的免疫反应对于开发联合疫苗是必要的。在本研究中,我们利用乙型肝炎病毒表面抗原(HBsAg)作为一种新型载体蛋白,结合荚膜多糖分子,开发了一种新型肺炎球菌结合疫苗。评估了该结合疫苗免疫小鼠后针对荚膜多糖和 HBsAg 的特异性抗体和 T 细胞免疫反应。此外,还分析了该结合疫苗在免疫小鼠中诱导的免疫细胞的独特基因谱。我们的结果表明,由肺炎 33F 荚膜多糖(Pn33Fps)与 HBsAg 结合而成的疫苗能够在体内诱导针对两种抗原的强烈特异性免疫反应。此外,与单一抗原接种相比,该结合疫苗在小鼠中诱导了更高表达与免疫激活相关的基因,以及更高的针对 Pn33Fps 和 HBsAg 的抗体滴度。对 Pn33Fps_HBs、Pn33Fps 或 HBsAg 免疫小鼠的免疫相关基因的动态表达变化分析表明,该结合疫苗具有强大的免疫原性。此外,对免疫小鼠器官的病理评估进一步表明该结合疫苗是安全的。总之,这些结果表明,由 Pn33Fps 与 HBsAg 组成的结合疫苗是一种新型有效的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cae/7156719/272726ff9fa2/41598_2020_62185_Fig1_HTML.jpg

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