Department of Medicine, University of Washington, Seattle, WA, USA.
Vaccine. 2011 Nov 3;29(47):8520-9. doi: 10.1016/j.vaccine.2011.09.046. Epub 2011 Sep 21.
HSV-2, the primary causative agent of genital herpes, establishes latency in sensory ganglia and reactivates causing recurrent lesions and viral shedding. Induction or expansion of CD4(+) and CD8(+) T cell responses are expected to be important for a successful therapeutic vaccine against HSV-2. A candidate vaccine consisting of 32 synthetic 35mer HSV-2 peptides non-covalently complexed with recombinant human Hsc70 protein (named HerpV, formerly AG-707) was tested for safety and immunogenicity in a Phase I study. These peptides are derived from 22 HSV-2 proteins representative of all phases of viral replication. Thirty-five HSV-2 infected participants were randomized and treated in one of four groups: HerpV+QS-21 (saponin adjuvant), HerpV, QS-21, or vehicle. The vaccine was well tolerated and safe. All seven participants with evaluable samples who were administered HerpV with QS-21 demonstrated a statistically significant CD4(+) T cell response to HSV-2 antigens, and the majority of such participants demonstrated a statistically significant CD8(+) T cell response as well. To our knowledge, this is the first candidate vaccine against HSV-2 to demonstrate a broad CD4(+) and CD8(+) T cell response in HSV-2(+) participants, and the first HSP-based vaccine to show immune responses against viral antigens in humans.
单纯疱疹病毒 2 型（HSV-2）是生殖器疱疹的主要病原体，它在感觉神经节中建立潜伏，并重新激活导致复发性病变和病毒脱落。诱导或扩增 CD4(+)和 CD8(+)T 细胞反应有望成为针对 HSV-2 的成功治疗性疫苗的重要因素。一种由 32 个合成的 35 mer HSV-2 肽与重组人 Hsc70 蛋白非共价复合而成的候选疫苗（名为 HerpV，前称 AG-707）在一项 I 期研究中进行了安全性和免疫原性测试。这些肽源自 22 种 HSV-2 蛋白，代表病毒复制的所有阶段。35 名 HSV-2 感染者被随机分为四组之一进行治疗：HerpV+QS-21（皂苷佐剂）、HerpV、QS-21 或载体。疫苗耐受性良好且安全。接受 HerpV+QS-21 治疗且有可评估样本的七名参与者均表现出针对 HSV-2 抗原的统计学显著的 CD4(+)T 细胞反应，且大多数此类参与者也表现出统计学显著的 CD8(+)T 细胞反应。据我们所知，这是第一个在 HSV-2 阳性参与者中证明针对 HSV-2 的广泛 CD4(+)和 CD8(+)T 细胞反应的 HSV-2 候选疫苗，也是第一个在人类中显示针对病毒抗原的 HSP 疫苗免疫反应的疫苗。
