Motin V L, de la Maza L M, Peterson E M
Department of Pathology, University of California-Irvine, Irvine, California 92697-4800, USA.
Clin Diagn Lab Immunol. 1999 May;6(3):356-63. doi: 10.1128/CDLI.6.3.356-363.1999.
C3H (H-2(k)) mice are susceptible to a vaginal challenge with human strains of Chlamydia trachomatis and thus are a useful strain for testing potential Chlamydia vaccine candidates. However, C3H mice are fairly poor responders in terms of the level of antibody resulting from immunization with potential protective peptides representing variable domains (VDs) of the major outer membrane protein (MOMP). C57BL/6 (H-2(b)) mice, on the other hand, are moderately resistant to a vaginal challenge but are good responders to the chlamydial MOMP VDs. Peptides representing universal T-cell helper epitopes were employed to determine whether the antibody response to a peptide representing VD4 of the MOMP, which has been shown to contain neutralizing epitopes, could be enhanced in C3H and C57 mice. Universal T-cell helper peptides from tetanus toxin, the pre-S2 region of hepatitis B virus, and the mouse heat shock protein 60, as well as the corresponding segment of the Chlamydia heat shock protein 60 (hspct), were coadministered with the VD4 peptide. Peptides were coencapsulated in liposomes containing the adjuvant monophosphoryl lipid A and administered by using a combination of mucosal and intramuscular injection. The only T-cell helper peptide that improved the immune response as judged by antibody level, in vitro neutralization assays, and T-cell proliferation was hspct. The response in the C57BL/6 strain was not significantly enhanced with hspct over levels achieved with VD4 alone; however, in C3H mice the levels of serum antibody to C. trachomatis increased to that seen in C57 mice. However, the molecular specificity and immunoglobulin subclass distribution differed from those of the C57 response, and the neutralizing titers and T-cell proliferation responses were lower. In both strains of mice, titers of vaginal antibody to C. trachomatis were low. In summary, of the T-helper peptides used, only hspct significantly enhanced the immune response of C3H mice to the VD4 peptide, but it had only a modest effect on the immune response of C57 mice.
C3H（H-2(k)）小鼠对人沙眼衣原体菌株的阴道攻击敏感，因此是测试潜在沙眼衣原体疫苗候选物的有用菌株。然而，就用代表主要外膜蛋白（MOMP）可变区（VD）的潜在保护性肽免疫产生的抗体水平而言，C3H小鼠的反应相当差。另一方面，C57BL/6（H-2(b)）小鼠对阴道攻击有中度抗性，但对衣原体MOMP VD反应良好。使用代表通用T细胞辅助表位的肽来确定在C3H和C57小鼠中，对已显示含有中和表位的MOMP的VD4肽的抗体反应是否可以增强。将来自破伤风毒素、乙肝病毒前S2区和小鼠热休克蛋白60的通用T细胞辅助肽，以及沙眼衣原体热休克蛋白60（hspct）的相应片段与VD4肽共同给药。肽被共包封在含有佐剂单磷酰脂质A的脂质体中，并通过粘膜和肌肉注射联合给药。根据抗体水平、体外中和试验和T细胞增殖判断，唯一能改善免疫反应的T细胞辅助肽是hspct。hspct对C57BL/6品系的反应增强不明显，未超过单独使用VD4时的水平；然而，在C3H小鼠中，沙眼衣原体血清抗体水平增加到C57小鼠中的水平。然而，分子特异性和免疫球蛋白亚类分布与C57反应不同，中和滴度和T细胞增殖反应较低。在两种品系的小鼠中，沙眼衣原体阴道抗体滴度都很低。总之，在所使用的T辅助肽中，只有hspct显著增强了C3H小鼠对VD4肽的免疫反应，但对C57小鼠的免疫反应只有适度影响。
