人/猴嵌合免疫缺陷病毒在中国源恒河猴体内的超感染免疫保护

Cross-protection against reinfection of simian-human immunodeficiency virus(SHIV)in Chinese macaques vaccinated with different types of SHIV

目的对于免疫缺陷病毒的天然感染是否可使机体产生有效的免疫保护仍在研究中,本研究旨在探索宿主通过天然感染获得免疫保护的机制。方法利用人/猴免疫缺陷嵌合病毒(SHIV)/中国源恒河猴动物感染模型,建立不同亚型SHIV在中国源恒河猴中的超感染模型,并通过病毒载量检测、结合抗体滴度及部分组的单基因组PCR测序分析(SGA),确认不同亚型及致病性的SHIV在体内的超感染保护效果并初步探讨相关的保护机制。结果两种SHIV毒株在中国源恒河猴体内的同源和异源超感染呈现出不同的保护效果,其中SHIV-CN97001初次感染,SHIV-KB9二次感染组检测到超感染的发生。同时中和抗体滴度与超感染免疫保护效果未表现出明显相关性,结合抗体在初次感染后略有下降,二次感染前后未出现明显变化,但总体抗体滴度较高。结论该发现说明不同特征的SHIV病毒在恒河猴体内可诱导出不同的超感染免疫保护效果,该模型为艾滋病毒免疫保护机制及疫苗的研究提供了良好的基础。

Objective To evaluate the cross-protective effects of simian-human immunodeficiency virus （SHIV） in Chinese macaques by vaccinating with different types of SHIVs. Methods A total of 12 adult Chi- nese rhesus monkeys were inoculated with pathogenic SHIV-KB9 or nowpathogenic SHIV-CN97001 virus strains and 4 control monkeys were left unimmunized. Thirty weeks later, all animals were exposed to SHIV- KB9 or SHIV-CN97001 that carries a heterologous or homologous envelope protein of the vaccine strain. Infection was monitored by measuring viral load, antibody response, and viral genomic RNA. Results Animals that were first challenged with SHIV-CN97001 and then with SHIV-KB9 showed new infections based on the results of virus single-genome amplification （SGA） PCR, while others showed no evidence of super-infection. All control animals without pre-vaccination became infected. There was no significant correla- tion between the susceptibility to super-infections and the neutralizing antibody levels at the time of exposure to the second time virus challenge. Conclusions SHIV infection may confer different levels of protection against a second time SHIV infection in Chinese monkeys. Understanding this protective response may assist HIV-1 vac- cine development.