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基于多态性蛋白 D 的异源初免-加强免疫接种可预防小鼠阴道沙眼衣原体感染。

Heterologous prime-boost vaccination based on Polymorphic protein D protects against intravaginal Chlamydia trachomatis infection in mice.

机构信息

Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, 5500, Mendoza, Argentina.

Experimental Immunology Laboratory, School of Biochemistry and Biological Sciences, National University of Litoral, Ciudad Universitaria, 3000, Santa Fe, Argentina.

出版信息

Sci Rep. 2022 Apr 22;12(1):6664. doi: 10.1038/s41598-022-10633-x.

DOI:10.1038/s41598-022-10633-x
PMID:35459778
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9030682/
Abstract

The control of the worldwide spread of sexually transmitted Chlamydia trachomatis (Ct) infection urgently demands the development of a preventive vaccine. In this work, we designed a vaccine based on a fragment of polymorphic protein D (FPmpD) that proved to be immunogenic enough to generate a robust systemic and mucosal IgG humoral immune response in two strains of mice. We used a heterologous prime-boost strategy, including simultaneous systemic and mucosal administration routes. The high titers of anti-PmpD antibodies elicited by this immunization scheme did not affect murine fertility. We tested the vaccine in a mouse model of Ct intravaginal infection. Anti-PmpD antibodies displayed potent neutralizing activity in vitro and protective effects in uterine tissues in vivo. Notably, the humoral immune response of PmpD-vaccinated mice was faster and stronger than the primary immune response of non-vaccinated mice when exposed to Ct. FPmpD-based vaccine effectively reduced Ct shedding into cervicovaginal fluids, bacterial burden at the genitourinary tract, and overall infectivity. Hence, the FPmpD-based vaccine might constitute an efficient tool to protect against Ct intravaginal infection and decrease the infection spreading.

摘要

控制性传播沙眼衣原体(Ct)感染的全球传播迫切需要开发预防性疫苗。在这项工作中,我们设计了一种基于多态性蛋白 D(FPmpD)片段的疫苗,该疫苗在两种小鼠品系中均具有足够的免疫原性,可以产生强大的系统和黏膜 IgG 体液免疫应答。我们使用了异源初免-加强策略,包括同时进行全身和黏膜给药途径。这种免疫方案引起的高滴度抗 PmpD 抗体不会影响小鼠的生育能力。我们在 Ct 阴道感染的小鼠模型中测试了该疫苗。抗 PmpD 抗体在体外显示出强大的中和活性,并在体内子宫组织中具有保护作用。值得注意的是,当接触 Ct 时,PmpD 疫苗接种小鼠的体液免疫反应比未接种疫苗小鼠的初次免疫反应更快、更强。基于 FPmpD 的疫苗可有效减少 Ct 脱落至宫颈阴道液中的量、生殖道的细菌负荷和整体感染性。因此,基于 FPmpD 的疫苗可能成为预防 Ct 阴道感染和减少感染传播的有效工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/dfdb7a2280fe/41598_2022_10633_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/60561b400a0d/41598_2022_10633_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/db24fd46d4cc/41598_2022_10633_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/4dbe7d09a53b/41598_2022_10633_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/6250ee1c1fc4/41598_2022_10633_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/e4f4f3167dc6/41598_2022_10633_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/20a0b1e6a1d5/41598_2022_10633_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/dfdb7a2280fe/41598_2022_10633_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/60561b400a0d/41598_2022_10633_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/e4548fc6afba/41598_2022_10633_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/db24fd46d4cc/41598_2022_10633_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/4dbe7d09a53b/41598_2022_10633_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/6250ee1c1fc4/41598_2022_10633_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/e4f4f3167dc6/41598_2022_10633_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/20a0b1e6a1d5/41598_2022_10633_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a7/9033793/dfdb7a2280fe/41598_2022_10633_Fig8_HTML.jpg

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