Institution of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China.
Department of Dermatology, The First Hospital of Changsha, Changsha, 410000, China.
Appl Microbiol Biotechnol. 2019 Jan;103(2):941-952. doi: 10.1007/s00253-018-9513-4. Epub 2018 Nov 23.
Chlamydia psittaci is an obligate intracellular pathogen with a broad host range that can lead to severe infectious disease by transferring from birds to humans. Vaccination has been considered the best way to prevent chlamydial infection; nevertheless, there is currently still no commercially available vaccine that can inhibit the spread of C. psittaci. In previous study, major outer membrane protein (MOMP) of C. psittaci was confirmed to be an appropriate candidate antigen for limiting C. psittaci respiratory infections in a murine model, and plasmid-encoded CPSIT_p6 also has functions similar to those of MOMP in our study. Therefore, according to bioinformatics analysis, we developed a recombinant peptide containing multiple antigenic epitopes from MOMP (24-32, 262-272) and CPSIT_p6 protein (109-119, 173-181) and evaluated the efficacy of peptide immunization. BALB/c mice were inoculated intraperitoneally with the recombinant multi-epitope antigens three times at 2-week intervals and subsequently intranasally infected with C. psittaci. We found that the recombinant multi-epitope antigens induced strong humoral and Th1 cellular immune responses by producing meaningfully high levels of antigen-specific antibodies, interferon-gamma (IFN-γ), or interleukin-2 (IL-2). Vaccination significantly reduced the bacterial burden and the degree of inflammation in the infected lungs and led to lower levels of IFN-γ and IL-6. Furthermore, adoptive transfer of CD4 splenocytes harvested from the vaccinated mice produced a significantly lower chlamydial load, indicating the importance of the cellular immune response. Therefore, the recombinant multi-epitope antigens may provide the basis for a new peptide-based vaccine against C. psittaci infection.
鹦鹉热衣原体是一种专性细胞内病原体,宿主范围广泛,可通过鸟类向人类传播而导致严重的传染病。疫苗接种被认为是预防衣原体感染的最佳方法;然而,目前仍然没有可商售的疫苗能够抑制鹦鹉热衣原体的传播。在之前的研究中,已经证实鹦鹉热衣原体的主要外膜蛋白(MOMP)是限制鼠模型中鹦鹉热衣原体呼吸道感染的合适候选抗原,并且在我们的研究中,质粒编码的 CPSIT_p6 也具有类似于 MOMP 的功能。因此,根据生物信息学分析,我们从 MOMP(24-32、262-272)和 CPSIT_p6 蛋白(109-119、173-181)中开发了一种含有多个抗原表位的重组肽,并评估了肽免疫的效果。BALB/c 小鼠每隔 2 周通过腹腔接种重组多表位抗原 3 次,然后通过鼻腔感染鹦鹉热衣原体。我们发现,重组多表位抗原通过产生具有重要意义的高水平抗原特异性抗体、干扰素-γ(IFN-γ)或白细胞介素-2(IL-2),诱导强烈的体液和 Th1 细胞免疫反应。接种疫苗显著降低了感染肺部的细菌负荷和炎症程度,并导致 IFN-γ和 IL-6 水平降低。此外,从接种疫苗的小鼠中分离的 CD4 脾细胞的过继转移产生了明显较低的衣原体负荷,表明细胞免疫反应的重要性。因此,重组多表位抗原可能为针对鹦鹉热衣原体感染的新型肽疫苗提供基础。