Macaques Vaccinated with Simian Immunodeficiency Virus SIVmac239Δnef Delay Acquisition and Control Replication after Repeated Low-Dose Heterologous SIV Challenge
Macaques Vaccinated with Simian Immunodeficiency Virus SIVmac239Δnef Delay Acquisition and Control Replication after Repeated Low-Dose Heterologous SIV Challenge
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DOI：
10.1128/jvi.00041-10
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发表时间：
2010-09-15
影响因子：
5.4
通讯作者：
Watkins, David I.
中科院分区：
文献类型：
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作者：
Reynolds, Matthew R.;Weiler, Andrea M.;Watkins, David I.
有效的人类免疫缺陷病毒（HIV）疫苗可能需要减少粘膜传播，并且在发生感染时控制病毒复制。为了确定我们最好的猿猴免疫缺陷病毒 (SIV) 疫苗是否能够实现这些崇高目标，我们给 8 只印度恒河猴接种了 SIVmac239 Delta nef 疫苗，并通过直肠内 (i.r.) 反复注射低剂量的致病性异源群体分离株 SIVsmE660 进行攻击。我们发现与初始对照相比，SIVsmE660 的获取显着减少（对数秩检验；P = 0.023）。经过 10 次粘膜攻击后，我们在 8 只接种疫苗的动物中仅 5 只检测到攻击菌株的复制。相比之下，在这 10 次挑战后，8 只对照动物中有 7 只感染了 SIVsmE660。此外，感染 SIVsmE660 的疫苗接种动物对急性病毒复制峰值的控制明显优于未接触过的对照组（Mann-Whitney U 检验；P = 0.038）。五名 SIVsmE660 疫苗接种者中的四名在感染后第 4 周迅速控制了病毒复制。不幸的是，这四只接种疫苗的动物中的两只在慢性感染阶段失去了对病毒复制的控制。对这些动物中循环病毒的批量序列分析表明，疫苗和攻击毒株之间发生了重组，并可能导致这些动物中病毒复制的增加。总体而言，我们的结果表明，精心设计的艾滋病毒疫苗可能既可以降低获得率，又可以控制病毒复制。
An effective human immunodeficiency virus (HIV) vaccine will likely need to reduce mucosal transmission and, if infection occurs, control virus replication. To determine whether our best simian immunodeficiency virus (SIV) vaccine can achieve these lofty goals, we vaccinated eight Indian rhesus macaques with SIVmac239 Delta nef and challenged them intrarectally (i.r.) with repeated low doses of the pathogenic heterologous swarm isolate SIVsmE660. We detected a significant reduction in acquisition of SIVsmE660 in comparison to that for naive controls (log rank test; P = 0.023). After 10 mucosal challenges, we detected replication of the challenge strain in only five of the eight vaccinated animals. In contrast, seven of the eight control animals became infected with SIVsmE660 after these 10 challenges. Additionally, the SIVsmE660-infected vaccinated animals controlled peak acute virus replication significantly better than did the naive controls (Mann-Whitney U test; P = 0.038). Four of the five SIVsmE660 vaccinees rapidly brought virus replication under control by week 4 postinfection. Unfortunately, two of these four vaccinated animals lost control of virus replication during the chronic phase of infection. Bulk sequence analysis of the circulating viruses in these animals indicated that recombination had occurred between the vaccine and challenge strains and likely contributed to the increased virus replication in these animals. Overall, our results suggest that a well-designed HIV vaccine might both reduce the rate of acquisition and control viral replication.