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腺病毒载体疫苗安全性得到证实

近日,国际著名疫苗学期刊《疫苗》(Vaccine)发表了中国科学院广州生物医药与健康研究院陈凌博士(客座研究员)指导的课题组的研究成果“Epidemiology of adenovirus type 5 neutralizing antibodies in healthy people and AIDS patients in Guangzhou, southern China”。该研究对广州地区健康人群和艾滋病病人体内预存5型腺病毒(Ad5)中和抗体情况进行了流行病学调查,证实了腺病毒载体疫苗的安全性。

腺病毒载体疫苗具有诸多优良的特性,曾被认为是疫苗研究中的希望之星,并在全球进入大规模的二期临床实验。但在2007年底,默克公司和艾滋病疫苗试验联盟(HVTN)联合宣布,由于未能有效预防艾滋病感染,该疫苗实验宣告终止。随后,有科学家认为人群中预存的Ad5中和抗体是该疫苗失败的一个原因,但预存Ad5抗体与艾滋病易感性到底有无相关性一直还未有定论。对此,陈凌课题组通过对广州地区进行了流行病学调查,结果表明绝大多数人都有自然感染过Ad5且比例随年龄的增长而增高。对正常人群和艾滋病感染人群之间的比较显示其Ad5的预存中和抗体发生率并没有统计学差异。这一结果及国际其它知名实验室的最新数据均表明:人体预存的Ad5抗体与艾滋病的易感性之间没有相关性,为Ad5作为疫苗载体的继续使用提供了重要的依据。

该项目由国家十一五科技重大专项、中国科学院、国家自然科学基金等经费资助。

 

英文论文摘要:

Epidemiology of adenovirus type 5 neutralizing antibodies in healthy people and AIDS patients in Guangzhou, southern China

Abstract

Recombinant adenovirus serotype 5 (Ad5) viruses have been extensively explored as vectors for vaccination or gene therapy. However, one major obstacle to their clinical application is the high prevalence of preexisting anti-Ad5 immunity resulting from natural infection. It has been reported that there are geographic variations in the prevalence of natural adenovirus infection. In the present study, we investigated the seroprevalence of Ad5 in Guangzhou, southern China by measuring the Ad5 neutralizing antibodies in blood samples collected from several sites. The seroprevalence was 77.34% in the general healthy population. The seroprevalence and antibody titers increased with age, with the older population (41-72 years old) having the highest seropositivity (84.8%) and percentage (54.4%) of high Ad5 neutralizing antibody titers (>1000). The dynamics of Ad5 neutralizing antibodies were stable and persistent over the course of eight months. Furthermore, the seroprevalence of Ad5 in the HIV-infected AIDS patients was investigated and there was no significant difference from the general healthy population. Our survey provides useful insights for the future development of Ad5-based vaccination and gene therapy.

Keywords: Adenovirus; Antibody; AIDS; HIV,vaccine

 

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