Wang B S, Search D J, Lumanglas A A, Ingling J, Corbett M J, Shieh H M, Kraft L A
Laboratory of Immunoendocrinology, Fort Dodge Animal Health, Cyanamid Agricultural Research Center, Princeton, New Jersey 08543-0400, USA.
Anim Biotechnol. 1998;9(1):21-33. doi: 10.1080/10495399809525889.
Antibodies generated against a synthetic growth hormone (GH) peptide in a number of animal species were shown to enhance the efficacy of GH. However, the ability to produce the effective antibodies diminished over the time and repeated boosters failed to overcome the hurdle. Therefore, this study was designed to address the issue on the fallen antibody responses by employing different GH peptide antigen preparations in cattle. Holstein steers were repeatedly immunized with a synthetic peptide corresponding to an amino acid sequence 54-95 of porcine GH (pGH). The peptide was conjugated to ovalbumin (OVA) as a carrier. Animals initially responded to the antigen well and elicited antibodies specific to the peptide. However, the 4th challenge with the same OVA-peptide antigen rendered animals unresponsive, resulting in a decline in antibody production. This unresponsiveness was overcome by switching the antigen at the 5th immunization from OVA-peptide to a recombinant peptide preparation which was composed of maltose binding protein (MBP) as a carrier. Antibodies generated in cattle after the 5th immunization recognized not only the pGH(54-95) peptide, but also bovine GH (bGH) and pGH. These antibodies were not immunoreactive with an unrelated control peptide. Hypophysectomized (hypox) rats were used for functional analysis and bGH was active in promoting the growth of these GH-deficient rats. The growth-promoting effect of bGH was significantly enhanced by mixing with bovine anti-peptide antibodies prior to administration. Therefore, the present findings suggest that peptide 54-95 induces cattle to elicit antibodies capable of not only recognizing bGH but also augmenting the somatogenic effectiveness of bGH in hypox rats.
在许多动物物种中，针对合成生长激素（GH）肽产生的抗体显示出能增强GH的功效。然而，产生有效抗体的能力会随着时间推移而减弱，且重复加强免疫也未能克服这一障碍。因此，本研究旨在通过在牛中使用不同的GH肽抗原制剂来解决抗体反应下降的问题。用对应于猪生长激素（pGH）氨基酸序列54 - 95的合成肽反复免疫荷斯坦公牛。该肽与作为载体的卵清蛋白（OVA）偶联。动物最初对该抗原反应良好，并产生了针对该肽的特异性抗体。然而，用相同的OVA - 肽抗原进行第4次攻击时，动物不再有反应，导致抗体产生下降。通过在第5次免疫时将抗原从OVA - 肽换成由麦芽糖结合蛋白（MBP）作为载体的重组肽制剂，克服了这种无反应性。第5次免疫后在牛中产生的抗体不仅识别pGH（54 - 95）肽，还识别牛生长激素（bGH）和pGH。这些抗体与无关的对照肽无免疫反应性。用垂体切除的（hypox）大鼠进行功能分析，bGH在促进这些生长激素缺乏大鼠的生长方面具有活性。在给药前将bGH与牛抗肽抗体混合，其促生长作用显著增强。因此，本研究结果表明，54 - 95肽能诱导牛产生不仅能识别bGH，还能增强bGH在hypox大鼠中促生长效力的抗体。
