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评价三种基于多态膜蛋白 D 的制剂在感染 的小鼠中的效果。

Evaluation of three formulations based on Polymorphic membrane protein D in mice infected with .

机构信息

Laboratorio de Bioquímica e Inmunidad, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas (IMBECUCONICET), Universidad Nacional de Cuyo, Mendoza, Argentina.

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

出版信息

Front Immunol. 2023 Nov 16;14:1267684. doi: 10.3389/fimmu.2023.1267684. eCollection 2023.

DOI:10.3389/fimmu.2023.1267684
PMID:38045697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10690417/
Abstract

The significant impact of infections worldwide highlights the need to develop a prophylactic vaccine that elicits effective immunity and protects the host from the immunopathological effects of infection. The aim of this study was to evaluate a vaccine based on a fragment of the Polymorphic membrane protein D (FPmpD) of as an immunogen using a heterologous DNA prime-protein boost strategy in female mice Three different formulations were evaluated as protein boost: free recombinant FPmpD (rFPmpD) or rFPmpD formulated with a liposomal adjuvant alternatively supplemented with CpG or a cationic lipopeptide as immunostimulants. The three candidates induced an increase in the cervicovaginal and systemic titers of anti-rFPmpD antibodies in two strains of mice (BALB/c and C57BL/6), with no evidence of fertility alterations. The three formulations induced a rapid and robust humoral immune response upon the challenge. However, the booster with free rFPmpD more efficiently reduced the shedding of infective and prevented the development of immunopathology. The formulations containing adjuvant induced a strong inflammatory reaction in the uterine tissue. Hence, the prime-boost strategy with the adjuvant-free FPmpD vaccine formulation might constitute a promissory candidate to prevent intravaginal infection.

摘要

的全球感染的重大影响突显了开发一种预防性疫苗的必要性,该疫苗能引发有效的免疫,并保护宿主免受感染的免疫病理影响。本研究的目的是评估一种基于多态性膜蛋白 D (FPmpD) 的疫苗片段作为免疫原,使用异源 DNA 初免-蛋白加强策略在雌性小鼠中进行评估。三种不同的制剂被评估为蛋白加强:游离重组 FPmpD (rFPmpD) 或用脂质体佐剂配制的 rFPmpD,或者用 CpG 或阳离子脂肽作为免疫刺激剂进行补充。这三种候选物在两种小鼠品系(BALB/c 和 C57BL/6)中引起了针对 rFPmpD 的宫颈阴道和全身抗体滴度的增加,没有证据表明生育力发生改变。这三种制剂在感染后迅速引发了强烈的体液免疫反应。然而,用游离 rFPmpD 进行的加强免疫更有效地减少了感染性的脱落,并防止了免疫病理学的发展。含有佐剂的制剂在子宫组织中引起强烈的炎症反应。因此,无佐剂的 FPmpD 疫苗制剂的初免-加强策略可能是预防阴道内感染的有前途的候选方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/564f65a89649/fimmu-14-1267684-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/be332d9449e2/fimmu-14-1267684-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/8ec5fb69b0e0/fimmu-14-1267684-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/a3ce5e31f425/fimmu-14-1267684-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/564f65a89649/fimmu-14-1267684-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/be332d9449e2/fimmu-14-1267684-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/f526108a68f7/fimmu-14-1267684-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/c6d8a8cbd909/fimmu-14-1267684-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/19651d72968d/fimmu-14-1267684-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/8ec5fb69b0e0/fimmu-14-1267684-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/a3ce5e31f425/fimmu-14-1267684-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3652/10690417/564f65a89649/fimmu-14-1267684-g007.jpg

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