Pal S, Theodor I, Peterson E M, de la Maza L M
Department of Pathology, Medical Sciences, University of California, Irvine 92697-4800, USA.
Vaccine. 1997 Apr;15(5):575-82. doi: 10.1016/s0264-410x(97)00206-5.
In order to analyze the protective role that IgA may play in a chlamydial infection two IgA monoclonal antibodies (mAb), MoPn 4-2 and MoPn 13-2, were raised against the major outer membrane protein (MOMP) of the Chlamydia trachomatis mouse pneumonitis (MoPn) biovar. mAb MoPn 4-2 was found to be serovar specific while mAb MoPn 13-2 was species specific. mAb MoPn 4-2 recognized a surface exposed conformational epitope as shown by its ability to bind to native EBs and nonreduced MOMP while failing to bind to heat and trypsin treated EBs, to reduced MOMP and to synthetic MOMP peptides. In contrast, mAb MoPn 13-2 recognized a nonconformational epitope since it was able to bind treated EBs, to reduced MOMP and to the synthetic peptide MTTWNPTISGSGI located in variable domain 4 of the MOMP. Both mAbs agglutinated intact EBs and had in vitro neutralizing activity. However, mAb MoPn 4-2 had a 20-fold higher in vitro neutralizing ability when compared to mAb MoPn 13-2 (50% neutralization at 5 micrograms ml-1 vs 100 micrograms ml-1). In an in vitro in vivo infectivity assay, mAb MoPn 4-2 protected mice against infertility when C. trachomatis MoPn elementary bodies were preincubated with the mAb before inoculation. In addition, passive transfer of mAb MoPn 4-2 resulted in significant protection as measured by a decrease in the number of mice infected, and in the intensity and duration of vaginal shedding. These results support previous findings suggesting that IgA antibodies can play a role in protection against a chlamydial infection, and further encourage work to develop vaccination strategies that elicit mucosal immunity.
为了分析IgA在衣原体感染中可能发挥的保护作用，制备了两种针对沙眼衣原体小鼠肺炎（MoPn）生物变种主要外膜蛋白（MOMP）的IgA单克隆抗体（mAb），即MoPn 4-2和MoPn 13-2。发现mAb MoPn 4-2具有血清型特异性，而mAb MoPn 13-2具有种特异性。mAb MoPn 4-2识别一个表面暴露的构象表位，这表现为它能够结合天然EBs和未还原的MOMP，而不能结合经加热和胰蛋白酶处理的EBs、还原的MOMP和合成的MOMP肽。相反，mAb MoPn 13-2识别一个非构象表位，因为它能够结合经处理的EBs、还原的MOMP以及位于MOMP可变区4的合成肽MTTWNPTISGSGI。两种mAb都能凝集完整的EBs并具有体外中和活性。然而，与mAb MoPn 13-2相比，mAb MoPn 4-2的体外中和能力高20倍（50%中和时分别为5微克/毫升和100微克/毫升）。在体外体内感染性试验中，当沙眼衣原体MoPn原体在接种前与mAb MoPn 4-2预孵育时，该mAb可保护小鼠免于不育。此外，通过感染小鼠数量的减少以及阴道排菌的强度和持续时间的降低来衡量，mAb MoPn 4-2的被动转移产生了显著的保护作用。这些结果支持了先前的研究发现，即IgA抗体可在预防衣原体感染中发挥作用，并进一步鼓励开展工作以开发能引发黏膜免疫的疫苗接种策略。
