DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge
DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge
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DOI：
10.1073/pnas.0902628106
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发表时间：
2009-09-15
影响因子：
11.1
通讯作者：
Pavlakis, George N.
中科院分区：
文献类型：
--
作者：
Rosati, Margherita;Bergamaschi, Cristina;Pavlakis, George N.
优化后的质粒dna编码大部分SIVmac239蛋白，并通过电穿孔（EP）传递，在恒河猴中引起了强烈的免疫反应。在致病性SIVmac251攻击后，疫苗接种降低了急性和慢性感染阶段的病毒血症。两组猕猴接种了产生不同抗原形式的DNA质粒，“天然”和“修饰”，诱导了不同的免疫反应。两组在感染急性期均表现出较低的病毒血症，而免疫组在感染慢性期表现出较好的保护作用（病毒载量降低1.7 log, P = 0.009）。两组对DNA疫苗抗原（包括Gag、Pol、Env、Nef和Tat）均产生了强烈的细胞和体液反应。疫苗接种诱导了中枢记忆和效应记忆T细胞，这些T细胞在攻击当天保持不变，表明在病毒攻击时具有快速动员的潜力。接受天然抗原的小组产生了更高更持久的抗env抗体，包括在挑战当天的中和抗体。这些结果表明，与在该猕猴模型中测试的任何其他疫苗模式相比，在没有任何异种增强的情况下接种DNA疫苗可以提供对高病毒血症的保护。
Optimized plasmid DNAs encoding the majority of SIVmac239 proteins and delivered by electroporation (EP) elicited strong immune responses in rhesus macaques. Vaccination decreased viremia in both the acute and chronic phases of infection after challenge with pathogenic SIVmac251. Two groups of macaques were vaccinated with DNA plasmids producing different antigen forms, "native'' and "modified,'' inducing distinct immune responses. Both groups showed significantly lower viremia during the acute phase of infection, whereas the group immunized with the native antigens showed better protection during the chronic phase (1.7 log decrease in virus load, P = 0.009). Both groups developed strong cellular and humoral responses against the DNA vaccine antigens, which included Gag, Pol, Env, Nef, and Tat. Vaccination induced both central memory and effector memory T cells that were maintained at the day of challenge, suggesting the potential for rapid mobilization upon virus challenge. The group receiving the native antigens developed higher and more durable anti-Env antibodies, including neutralizing antibodies at the day of challenge. These results demonstrate that DNA vaccination in the absence of any heterologous boost can provide protection from high viremia comparable to any other vaccine modalities tested in this macaque model.