Immunization with an acellular vaccine consisting of the outer membrane complex of Chlamydia trachomatis induces protection against a genital challenge
Immunization with an acellular vaccine consisting of the outer membrane complex of Chlamydia trachomatis induces protection against a genital challenge
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DOI：
10.1128/iai.65.8.3361-3369.1997
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发表时间：
1997-08-01
影响因子：
3.1
通讯作者：
delaMaza, LM
中科院分区：
文献类型：
--
作者：
Pal, S;Theodor, I;delaMaza, LM
用三种沙眼衣原体小鼠肺炎（MoPn）主要外膜蛋白（MOMP）制剂以及由衣原体外膜复合物（COMC）组成的无细胞疫苗在BALB/c雌性小鼠中研究了诱导针对生殖器攻击的保护能力。MOMP制剂用三种不同类型的去污剂十二烷基硫酸钠（SDS）、正辛基-β-D-吡喃葡萄糖苷（OGP）、和Zwittergent 3-14（Z3-14），阳性免疫对照由鼻内接种10（4）C的小鼠组成。沙眼衣原体MoPn包涵体形成单位（IFU），接种卵清蛋白的小鼠作为阴性对照，此外，包括假免疫的未攻击组作为生育力对照。最后一次免疫后两周，在小鼠左侧卵巢囊中用10（5）C，沙眼衣原体MoPn IFU攻击，收集阴道拭子用于培养，测定阴道和血清样品的衣原体特异性抗体，并收集脾细胞以确定淋巴增殖反应。攻毒后42天，将小鼠与经证实的雄性育种小鼠交配，处死认为妊娠的动物（根据体重确定），并对胚胎进行计数。结果表明，接种衣原体抗原的小鼠均产生了明显的体液免疫和细胞免疫应答，血清中均检测到抗MOMP可变区（VD）1的抗体。然而，仅在用Z3-14-MOMP和COMC免疫的组中检测到针对VD 3和VD 4的抗体。用COMC免疫的小鼠在阴道中产生显著的免疫球蛋白A衣原体特异性抗体，而用洗涤剂提取的MOMP免疫的小鼠的抗体滴度较低。在用COMC免疫的小鼠中观察到阴道脱落的强度和持续时间显著降低，在用OGP-MOMP免疫的组中观察到中度降低。在用SDS-和Z3-14-MOMP免疫的动物组中未观察到针对感染的保护。此外，在用COMC制备物免疫的小鼠中，仅25%（4/20）的小鼠脱落C。阴道培养法检测沙眼衣原体的阳性率为83%（40/48），而对照组卵清蛋白组培养阳性率为83%（40/48）（P < 0.05）。此外，交配后，发现接种COMC的小鼠的生育率与对照假免疫、未攻毒的动物相当（分别为70% [14/20]和81% [17/21][P > 0.05]），两组中每只小鼠的平均胚胎数无显著差异与此相反，用纯化的MOMP制剂免疫的小鼠不能抵抗不育。总之，COMC制剂保护小鼠抵抗感染和不育，支持开发抗C.沙眼感染
The ability to induce protection against a genital challenge was studied in BALB/c female mice with three Chlamydia trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) preparations as well as an acellular vaccine consisting of the chlamydial outer membrane complex (COMC), The MOMP preparations were extracted with three different types of detergents, sodium dodecyl sulfate (SDS), n-octyl-beta-D-glucopyranoside (OGP), and Zwittergent 3-14 (Z3-14), A positive immunization control consisted of mice inoculated intranasally with 10(4) C. trachomatis MoPn inclusion-forming units (IFU), Mice inoculated with ovalbumin served as a negative control, Furthermore, a sham-immunized, nonchallenged group was included as a fertility control, Two weeks after the last immunization, the mice were challenged in the left ovarian bursa with 10(5) C, trachomatis MoPn IFU, Vaginal swabs were collected for culture, vaginal and serum samples were assayed for chlamydial-specific antibodies, and splenocytes were collected to determine the lymphoproliferative response. At 42 days after the challenge, the mice were mated with proven male breeder mice, Animals that were considered to be pregnant (as determined by weight) were killed, and the embryos were counted. A significant humoral and cell-mediated immune response was observed in all the groups of mice inoculated with chlamydial antigens, Antibodies to variable domain (VD)1 of the MOMP were detected in serum samples from all the immunized groups. However, antibodies to VD3 and VD4 were detected only in the groups immunized with the Z3-14-MOMP and the COMC, Mice immunized with COMC developed significant immunoglobulin A chlamydia-specific antibodies in the vagina, while mice immunized with the detergent-extracted MOMPs had low antibody titers, Following the intrabursal challenge, a significant decrease in the intensity and duration of vaginal shedding was noted in the mice immunized with COMC and a moderate decrease was noted in the group immunized with OGP-MOMP. No protection against the infection was noted in the groups of animals immunized with SDS- and Z3-14-MOMP. Furthermore, of the mice immunized with the COMC preparation, only 25% (4 of 20) shed C. trachomatis, as determined by vaginal culture, while 83% (40 of 48) of the control mice inoculated with ovalbumin were culture positive (P < 0.05). In addition, after mating, the mice inoculated with COMC were found to have fertility rates comparable to those of the control sham-immunized, nonchallenged animals (70% [14 of 20] versus 81% [17 of 21], respectively [P > 0.05]), and there were no significant differences between the average number of embryos per mouse in the two groups (5.1 versus 5.9, respectively [P > 0.05]), In contrast, mice immunized with the purified MOMP preparations were not protected against infertility, In summary, a preparation of the COMC protected mice against infection and infertility, supporting the feasibility of the development of an acellular vaccine against C. trachomatis infections.