Kaliyaperumal A, Chauhan V S, Talwar G P, Raghupathy R
Department of Medicine, University Medical School, Chicago, USA.
Eur J Immunol. 1995 Dec;25(12):3375-80. doi: 10.1002/eji.1830251226.
In the course of clinical trials on a birth control vaccine, it was found that some of the immunized women responded poorly to booster immunizations. This vaccine consists of a dimer of the beta chain of human chorionic gonadotropin (beta hCG) and the alpha chain of ovine luteinizing hormone (alpha oLH), linked to tetanus toxoid (TT) as a carrier. Changing this carrier to diphtheria toxoid resulted in reversion to high anti-hCG antibody titers, indicating the extent to which the carrier influences anti-ligand responses in this system. The suppression of anti-hCG responses after booster immunizations was reminiscent of the phenomenon of carrier-induced, epitope-specific regulation. In a mouse model designed to test the effects of preimmunization with TT on anti-hCG responses, we found that a single preimmunization with TT causes reduced anti-hCG antibody responses in two out of four mouse strains, while anti-alpha oLH antibody responses were not affected by the preimmunization with TT. This is particularly interesting considering that beta hCG and alpha oLH were not presented when linked separately to TT. In an effort to devise a strategy to circumvent this carrier-induced, ligand-specific hyporesponsiveness, we investigated the effectiveness of a synthetic T helper epitope from TT as carrier. We show that preimmunization with TT causes a less profound reduction in anti-hCG titers if the preimmunized mice are subsequently injected with alpha oLH-beta hCG conjugated to a synthetic tetanus toxin peptide recognized by TT-induced and peptide-induced T cells.
在一种避孕疫苗的临床试验过程中，发现一些接种疫苗的女性对加强免疫的反应不佳。这种疫苗由人绒毛膜促性腺激素β链（β-hCG）的二聚体和绵羊促黄体生成素α链（α-oLH）组成，与破伤风类毒素（TT）作为载体相连。将这种载体换成白喉类毒素后，抗hCG抗体滴度恢复到高水平，这表明载体在该系统中对抗配体反应的影响程度。加强免疫后抗hCG反应的抑制让人联想到载体诱导的表位特异性调节现象。在一个旨在测试用TT进行预免疫对抗hCG反应影响的小鼠模型中，我们发现用TT进行单次预免疫会导致四种小鼠品系中的两种抗hCG抗体反应降低，而抗α-oLH抗体反应不受TT预免疫的影响。考虑到β-hCG和α-oLH分别与TT相连时不会出现这种情况，这一点尤其有趣。为了设计一种策略来规避这种载体诱导的配体特异性低反应性，我们研究了来自TT的合成T辅助表位作为载体的有效性。我们发现，如果给预先用TT免疫的小鼠随后注射与一种由TT诱导和肽诱导的T细胞识别的合成破伤风毒素肽偶联的α-oLH-β-hCG，那么用TT进行预免疫对抗hCG滴度的降低作用就不那么明显。
