Reduction of peak viremia by an integration-defective SIV proviral DNA vaccine in rhesus macaques
Reduction of peak viremia by an integration-defective SIV proviral DNA vaccine in rhesus macaques
复制标题
整合缺陷型 SIV 前病毒 DNA 疫苗可降低恒河猴病毒血症峰值
DOI：
10.1111/1348-0421.12744
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发表时间：
2019-10-14
影响因子：
2.6
通讯作者：
Gao，Feng
中科院分区：
文献类型：
--
作者：
Wang，Chu;Gao，Nan;Gao，Feng
一种整合酶缺陷SIV （idSIV）疫苗通过DNA启动物和病毒颗粒增强方法递送，可以在静脉注射SIVmac239攻击后的急性感染阶段抑制病毒载量（VLs）。本研究探讨了idSIV DNA和病毒颗粒单独免疫如何在SIV攻击后抑制中国恒河猴的VLs。两只猕猴用idSIV DNA免疫5次，两只猕猴用idSIV病毒颗粒免疫3次。免疫接种后，测量了接种后猕猴的细胞和体液免疫反应。静脉注射SIVmac239后28周监测vl和CD4+T细胞计数。SIV特异性T细胞反应仅在接种DNA疫苗的猕猴中检测到。然而，与DNA免疫的猕猴相比，用病毒颗粒免疫的猕猴对自体和异源病毒的结合和中和抗体稍好。攻毒后，DNA组的平均峰值病毒血症比对照组低2.3 log，而病毒颗粒免疫组与对照组的峰值病毒血症相似。各组CD4+T细胞计数相近。这些结果表明，idSIV DNA单独免疫可降低猕猴SIV攻击后急性感染期间的VLs，并可能作为与其他免疫原联合使用作为预防性疫苗的关键组成部分。
An integrase‐defective SIV (idSIV) vaccine delivered by a DNA prime and viral particle boost approach can suppress viral loads (VLs) during the acute infection stage after intravenous SIVmac239 challenge. This study investigated how idSIV DNA and viral particle immunization alone contributed to the suppression of VLs in Chinese rhesus macaques after SIV challenge. Two macaques were immunized with idSIV DNA five times and two macaques were immunized with idSIV viral particles three times. Cellular and humoral immune responses were measured in the vaccinated macaques after immunization. The VLs and CD4+T cell counts were monitored for 28 weeks after the intravenous SIVmac239 challenge. The SIV‐specific T cell responses were only detected in the DNA‐vaccinated macaques. However, binding and neutralizing antibodies against autologous and heterologous viruses were moderately better in macaques immunized with viral particles than in macaques immunized with DNA. After the challenge, the mean peak viremia in the DNA group was 2.3 logs lower than that in the control group, while they were similar between the viral particle immunization and control groups. Similar CD4+T cell counts were observed among all groups. These results suggest that idSIV DNA immunization alone reduces VLs during acute infection after SIV challenge in macaques and may serve as a key component in combination with other immunogens as prophylactic vaccines.