Induction of protection against vaginal shedding and infertility by a recombinant Chlamydia vaccine

Induction of protection against vaginal shedding and infertility by a recombinant Chlamydia vaccine
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DOI:
10.1016/j.vaccine.2011.05.013
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发表时间:
2011-07-18
期刊:
影响因子:
5.5
通讯作者:
de la Maza, Luis M.
de la Maza, Luis M.
中科院分区:
医学3区
文献类型:
--
作者:
Carmichael, Jennifer R.;Pal, Sukumar;de la Maza, Luis M.

文献摘要

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用衣原体重组主要外膜蛋白和佐剂CpG和Montanide配制的疫苗,测试了其保护BALB/c小鼠免受阴道攻击的能力。小鼠经阴道黏膜免疫。加结肠(Col.)或鼻腔(I.N.)加舌下(s.l.)],或全身[肌肉内(i.m.)加皮下(S.C.)]途径,以及粘膜启动和全身增强途径的组合。阴性对照组接种淋球菌孢子蛋白B(Ng-rPorB),阳性对照组鼻腔接种活衣原体。衣原体特异性体液免疫和细胞免疫反应在黏膜免疫和全身免疫联合免疫的人群中观察到最强。在阴道攻击后,使用粘膜预接剂和系统免疫组的小鼠阴道培养阳性的小鼠数量显著减少。例如,免疫的小鼠中,I.N./s.l。+I.M./S.C.,在实验的六周内,24%的人有阳性培养,而用Ng-rPorB免疫的阴性对照组有69%的培养阳性(P<0.05)。同样,与Ng-rPorB动物相比,由粘膜途径引发并由全身途径增强的一组小鼠在阴道培养中的IFU显著较少(P<0.05)。这些联合组也被保护免受不孕不育的影响。两组的生育率均为100%(I.N./S.L.+I.M./S.C.)和81%(i.vg./col.+I.M./S.C.)相当于用活衣原体免疫组(100%受精率;P>0.05)。这些结果表明了疫苗接种时间表和途径的重要性,并代表了第一项表明衣原体重组亚单位疫苗对不孕症具有保护作用的研究。(C)2011爱思唯尔有限公司。保留所有权利。
A vaccine formulated with the Chlamydia muridarum recombinant major outer membrane protein, plus the adjuvants CpG and Montanide, was tested for its ability to protect BALB/c mice against a vaginal challenge. Mice were immunized by mucosal [intravaginal (i.vag.) plus colonic (col.), or intranasal (i.n.) plus sublingual (s.l.)], or systemic [intramuscular (i.m.) plus subcutaneous (s.c.)] routes, and a combination of mucosal priming and systemic boosting routes. A negative control group was vaccinated with the Neisseria gonorrhoeae porin B (Ng-rPorB) and a positive control group was inoculated in the nares with live Chlamydia. The strongest Chlamydia-specific humoral and cell-mediated immune responses were observed in the groups immunized by a combination of mucosal and systemic routes. Following the vaginal challenge, groups immunized using mucosal priming followed by systemic immunization had a significant decrease in the number of mice with positive vaginal cultures. For example, of the mice immunized i.n./s.l. + i.m./s.c., 24% had positive cultures during the six weeks of the experiment versus 69% for the negative control group immunized with Ng-rPorB (P < 0.05). Similarly, the groups of mice primed by the mucosal routes and boosted by the systemic routes had significantly less IFU in the vaginal cultures when compared to the Ng-rPorB animals (P < 0.05). These combination groups were also protected against infertility. The two groups had fertility rates of 100% (i.n./s.l. + i.m./s.c.) and 81% (i.vag./col. + i.m./s.c.) equivalent to the positive-control group immunized with live Chlamydia (100% fertility; P > 0.05). These results show the importance of the schedule and routes of vaccination and represent the first study to show protection against infertility by a Chlamydia recombinant subunit vaccine. (C) 2011 Elsevier Ltd. All rights reserved.