A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge
A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge
复制标题
DOI：
10.1111/imm.12520
复制
发表时间：
2015-11-01
期刊：
影响因子：
6.4
通讯作者：
de la Maza, Luis M.
中科院分区：
文献类型：
--
作者：
Pal, Sukumar;Tatarenkova, Olga V.;de la Maza, Luis M.
C3 H/HeN雌性小鼠用天然鼠衣原体主要外膜蛋白（MOMP）接种，使用Montanide+CpG或Alum+CpG作为佐剂。阴性对照组用卵清蛋白（OVA）和相同佐剂免疫。作为阳性对照，小鼠鼻内接种活衣原体。用10（5）个小鼠隐孢子虫包涵体形成单位在卵巢囊中激发小鼠。生殖器激发后6周，将动物与雄性小鼠关在一起，并监测妊娠情况。接种MOMP+Montanide+CpG的小鼠产生了高水平的小鼠衣原体特异性抗体，具有高IgG 2a/IgG 1比率和中和滴度。使用明矾+CpG免疫的动物具有低抗体水平。当与阴性对照相比时，在用MOMP和Montanide+CpG接种的小鼠中细胞免疫应答显著更高，但用Alum+CpG接种的小鼠中不显著更高。在生殖器攻击后，用MOMP+CpG+Montanide免疫的小鼠中仅20%（4/20）具有阳性阴道培养物，而用MOMP+CpG+明矾免疫的小鼠中100%（9/9）具有阳性培养物。在接种活衣原体的阳性对照动物中，仅15%（3/20）的阴道培养物呈阳性。相反，用OVA+CpG+Montanide或最小必需培养基免疫的小鼠100%（20/20）具有阳性培养物。交配后，80%（16/20）的MOMP+CpG+Montanide接种小鼠和85%（17/20）的鼻内接种活鼠隐孢子虫的动物在两个子宫角中携带胚胎。在用MOMP和CpG+明矾或OVA免疫的小鼠中没有观察到针对不育的保护。总之，这是第一次，亚单位疫苗已被证明引发保护性免疫反应，在高度敏感的C3 H/HeN品系的小鼠对上生殖器的挑战。
C3H/HeN female mice were vaccinated with native Chlamydia muridarum major outer membrane protein (MOMP), using Montanide+CpG or Alum+CpG as adjuvants. Negative control groups were immunized with ovalbumin (OVA) and the same adjuvants. As positive control, mice were inoculated intranasally with live Chlamydia. Mice were challenged in the ovarian bursa with 10(5)C.muridarum inclusion forming units. Six weeks after the genital challenge the animals were caged with male mice and monitored for pregnancy. Mice vaccinated with MOMP+Montanide+CpG developed high levels of C.muridarum-specific antibodies, with a high IgG2a/IgG1 ratio and neutralizing titres. Animals immunized using Alum+CpG had low antibody levels. Cellular immune responses were significantly higher in mice vaccinated with MOMP and Montanide+CpG, but not with Alum+CpG, when compared with negative controls. Following the genital challenge, only 20% (4/20) of mice vaccinated with MOMP+CpG+Montanide had positive vaginal cultures whereas 100% (9/9) of mice immunized with MOMP+CpG+Alum had positive cultures. Of the positive control animals inoculated with live Chlamydia only 15% (3/20) had positive vaginal cultures. In contrast, 100% (20/20) of mice immunized with OVA+CpG+Montanide, or minimal essential medium, had positive cultures. Following mating, 80% (16/20) of mice vaccinated with MOMP+CpG+Montanide, and 85% (17/20) of animals inoculated intranasally with live C.muridarum carried embryos in both uterine horns. No protection against infertility was observed in mice immunized with MOMP and CpG+Alum or OVA. In conclusion, this is the first time that a subunit vaccine has been shown to elicit a protective immune response in the highly susceptible C3H/HeN strain of mice against an upper genital challenge.