A therapeutic HIV vaccine using coxsackie-HIV recombinants: A possible new strategy
A therapeutic HIV vaccine using coxsackie-HIV recombinants: A possible new strategy
复制标题
DOI：
10.1089/088922200750006074
复制
发表时间：
2000-10-01
影响因子：
1.5
通讯作者：
Ramsingh, AI
中科院分区：
文献类型：
--
作者：
Halim, SS;Collins, DN;Ramsingh, AI
治疗艾滋病毒感染者的最终目标是防止疾病进展。实现这一目标的策略是使用化疗来减少病毒载量，然后使用免疫疗法来刺激在长期无症状个体中观察到的HIV特异性免疫应答。表达HIV序列的有效的活重组病毒将能够诱导CTL和CD 4（+）辅助性T细胞应答。为了实现这些目标，病毒载体必须是免疫原性的，但在T细胞缺陷型宿主中保留其无毒表型。我们已经确定了一个柯萨奇病毒的变种，CB 4-P，可以诱导保护性免疫力对一个有毒的变种。此外，CB 4-P变体在缺乏CD 4（+）辅助T细胞的小鼠中保持无毒力，这表明CB 4-P可能是唯一适合作为治疗性HIV疫苗的病毒载体。采用两种诱导CTL和CD 4（+）辅助性T细胞应答的策略构建CB 4-P/HIV重组体。重组病毒是活的，遗传稳定的，并保留了亲本病毒的无毒表型。在设计用于疫苗开发的病毒载体时，必须解决的问题是先前存在的对载体的免疫是否会影响重组病毒的后续施用。使用测试重组体，我们表明先前暴露于亲本CB 4-P病毒并不影响重组体诱导针对外源序列的CD 4（+）T细胞应答的能力。结果表明，科萨基/艾滋病病毒重组的“鸡尾酒”可能是有用的治疗艾滋病病毒疫苗。
The ultimate goal in the treatment of HIV-infected persons is to prevent disease progression. A strategy to accomplish this goal is to use chemotherapy to reduce viral load followed by immunotherapy to stimulate HIV-specific immune responses that are observed in long-term asymptomatic individuals. An effective, live, recombinant virus, expressing HIV sequences, would be capable of inducing both CTL and CD4(+) helper T cell responses. To accomplish these goals, the viral vector must be immunogenic yet retain its avirulent phenotype in a T cell-deficient host. We have identified a coxsackievirus variant, CB4-P, that can induce protective immunity against a virulent variant. In addition, the CB4-P variant remains avirulent in mice lacking CD4(+) helper T cells, suggesting that CB4-P may be uniquely suited as a viral vector for a therapeutic HIV vaccine. Two strategies designed to elicit CTL and CD4(+) helper T cell responses were used to construct CB4-P/HIV recombinants. Recombinant viruses were viable, genetically stable, and retained the avirulent phenotype of the parental virus. In designing a viral vector for vaccine development, an issue that must be addressed is whether preexisting immunity to the vector would affect subsequent administration of the recombinant virus. Using a test recombinant, we showed that prior exposure to the parental CB4-P virus did not affect the ability of the recombinant to induce a CD4(+) T cell response against the foreign sequence. The results suggest that a "cocktail" of coxsackie/HIV recombinants may be useful as a therapeutic HIV vaccine.