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用恶性疟原虫无性血液期合成肽抗原接种的夜猴的肾脏病理学

Renal pathology in owl monkeys vaccinated with Plasmodium falciparum asexual blood-stage synthetic peptide antigens.

作者信息

Nagatake T, Broderson J R, Tegoshi T, Collins W E, Aikawa M

机构信息

Institute of Pathology, Case Western Reserve University, Cleveland, Ohio.

出版信息

Am J Trop Med Hyg. 1992 Nov;47(5):614-20. doi: 10.4269/ajtmh.1992.47.614.

Abstract

Renal specimens from Aotus monkeys were studied by light microscopy and immunohistochemistry to examine pathologic changes following vaccination with synthetic peptides corresponding to the 35-kD, 55-kD, and 83-kD asexual blood stage antigens of Plasmodium falciparum. The monkeys were vaccinated and later challenged with P. falciparum. In the monkeys vaccinated with Centers for Disease Control peptides (group I), specimens from four of six postvaccinated animals had mild to severe mesangial proliferation and two had diffuse interstitial nephritis. Specimens from three monkeys vaccinated with Colombia peptides (group II) had mild to severe mesangial proliferation and one had interstitial nephritis. In the hybrid polymer-vaccinated monkeys (group III), specimens from three animals had mild to moderate mesangial proliferation and one had severe interstitial nephritis. On the other hand, the control group immunized with bovine serum albumin (group IV) showed that specimens from three animals had mild to severe mesangial proliferation and two had severe interstitial nephritis. In the nonimmunized group (group V), specimens from three animals had moderate to severe mesangial proliferation and two had severe and mild interstitial nephritis. Immunohistochemical analysis using the peroxidase-antiperoxidase method revealed mesangial deposits of P. falciparum antigens in 11 of 14 vaccinated monkeys and in five of 10 unvaccinated controls. These results show that treatment of monkeys with prospective malaria vaccines does not increase the frequency of occurrence or of the severity of renal lesions. These data thus provide a baseline for assessing the safety of synthetic malarial vaccines in the future.

摘要

对夜猴的肾脏标本进行了光学显微镜检查和免疫组织化学研究,以检测用对应于恶性疟原虫35-kD、55-kD和83-kD无性血液期抗原的合成肽接种疫苗后的病理变化。给这些猴子接种疫苗,随后用恶性疟原虫进行攻击。在接种美国疾病控制中心肽的猴子(第一组)中,6只接种疫苗后的动物中有4只的标本出现轻度至重度系膜增生,2只出现弥漫性间质性肾炎。接种哥伦比亚肽的3只猴子(第二组)的标本出现轻度至重度系膜增生,1只出现间质性肾炎。在接种混合聚合物疫苗的猴子(第三组)中,3只动物的标本出现轻度至中度系膜增生,1只出现严重间质性肾炎。另一方面,用牛血清白蛋白免疫的对照组(第四组)显示,3只动物的标本出现轻度至重度系膜增生,2只出现严重间质性肾炎。在未免疫组(第五组)中,3只动物的标本出现中度至重度系膜增生,2只出现严重和轻度间质性肾炎。使用过氧化物酶-抗过氧化物酶方法进行的免疫组织化学分析显示,在14只接种疫苗的猴子中有11只以及10只未接种疫苗的对照中有5只出现恶性疟原虫抗原的系膜沉积。这些结果表明,用前瞻性疟疾疫苗治疗猴子不会增加肾损伤的发生频率或严重程度。因此,这些数据为未来评估合成疟疾疫苗的安全性提供了一个基线。

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