Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors
Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors
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DOI：
10.1128/jvi.75.16.7435-7452.2001
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发表时间：
2001-08-01
影响因子：
5.4
通讯作者：
Andino, R
中科院分区：
文献类型：
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作者：
Crotty, S;Miller, CJ;Andino, R
在这里，我们提供了第一份报告的保护，对阴道的挑战与高毒性猴免疫缺陷病毒（SIV）通过使用疫苗载体。构建了基于Sabin I和2株疫苗株病毒的新型脊髓灰质炎病毒载体，并使用这些载体产生了一系列在重叠片段中含有SIV gag、pol、env、nef和tat的新型病毒。将20种转基因脊髓灰质炎病毒（SabRV1-SIV和SabRV2-SIV）的两种混合物接种到7只食蟹猴中。所有猴均产生大量抗SIV血清和粘膜抗体应答。SIV特异性细胞毒性T淋巴细胞反应，检测到三个7猴接种疫苗后。所有7只接种疫苗的猕猴以及12只对照猕猴用致病性SIVmac251阴道攻击。引人注目的是，7只接种疫苗的动物中有4只表现出对阴道SIV攻击的实质性保护。所有12只对照猴均为SIV阳性。在7只接种SabRV-SIV疫苗的猴子中，有2只在攻击后没有发现感染的病毒学证据，表明这两只猴子完全受到保护。另外两只接种SabRV-SIV疫苗的猴子表现出急性后病毒血症明显减少至<10（3）拷贝/ml，表明疫苗引发了有效的细胞免疫应答。在攻毒后48周，6只对照动物中有3只出现临床AIDS。相比之下，根据所有临床参数判断，所有7只接种疫苗的猴均保持健康。这些结果证明了SabRV作为潜在的人疫苗载体的功效，并且它们表明使用表达一系列确定的抗原序列的疫苗载体混合物可以是远交群体中的有效疫苗接种策略。
Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector. New poliovirus vectors based on Sabin I and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag, pol, env, nef, and tat in overlapping fragments. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV were inoculated into seven cynomolgus macaques. All monkeys produced substantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte responses were detected in three of seven monkeys after vaccination. All 7 vaccinated macaques, as well as 12 control macaques, were challenged vaginally with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge. All 12 control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated monkeys we found no virological evidence of infection following challenge, indicating that these two monkeys were completely protected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to < 10(3) copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six control animals developed clinical AIDS by 48 weeks postchallenge. In contrast, all seven vaccinated monkeys remained healthy as judged by all clinical parameters. These results demonstrate the efficacy of SabRV as a potential human vaccine vector, and they show that the use of a vaccine vector cocktail expressing an array of defined antigenic sequences can be an effective vaccination strategy in an outbred population.