Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Curr Med Chem. 2011;18(26):3981-6. doi: 10.2174/092986711796957211.
The HIV pandemic continues to be a public health crisis with over 30 million people currently living with the disease and, depending on the estimate, another 2 - 2.8 million infected annually. The disappointing results of the first Phase II study of a highly immunogenic adenovirus-vectored vaccine, named the STEP trial, was a wake up call to both the clinical and preclinical HIV vaccine fields. A vaccine designed only to elicit T cells and including a single HIV gene insert, will not be sufficient to reduce transmission or lower viremia in people. Additionally, future use of adenovirus-based vectored vaccines needs to be carefully planned with respect to vector type, gene inserts, route of immunization and risk factors among subject volunteers. The initial observation of a transient, increased risk of infection in Ad5 seropositive, uncircumcised men who have sex with men (MSM) is still unexplained, and may yet be considered simply a random event. The vaccine field has not given up on adenoviruses and there is continued interest in pursuing these highly immunogenic vectors, either in combination approaches with DNA, use of rare serotypes with low seroprevalence, or those derived from simian origin. Finally, evaluation of replicating adenovirus vectors known to be capable of inducing potent cellular, humoral, and mucosal immunity will be vital to meeting our future goal of an effective HIV vaccine.
艾滋病大流行仍是一个公共卫生危机，目前有超过 3000 万人患有这种疾病，而且每年还有 200 万至 280 万人感染。名为 STEP 试验的高度免疫原性腺病毒载体疫苗的首次 II 期研究结果令人失望，这给临床和临床前 HIV 疫苗领域敲响了警钟。一种仅能引发 T 细胞反应并包含单个 HIV 基因插入物的疫苗，不足以降低病毒传播或降低人体中的病毒载量。此外，未来使用基于腺病毒的载体疫苗需要在载体类型、基因插入物、免疫途径和受试者志愿者中的风险因素等方面进行仔细规划。在 Ad5 血清阳性、未割包皮的男男性行为者（MSM）中观察到的感染风险短暂增加的最初观察结果仍然无法解释，并且可能仍被认为只是一个随机事件。疫苗领域并未放弃腺病毒，并且仍有兴趣继续研究这些具有高度免疫原性的载体，无论是与 DNA 的联合方法、使用血清流行率低的罕见血清型，还是源自灵长类动物的血清型。最后，评估已知能够诱导强烈的细胞、体液和黏膜免疫的复制型腺病毒载体对于实现我们未来有效 HIV 疫苗的目标至关重要。
