Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Vaccine. 2010 May 21;28(23):3963-71. doi: 10.1016/j.vaccine.2010.03.046. Epub 2010 Apr 9.
An HIV Env immunogen capable of eliciting broad immunity is critical for a successful vaccine. We constructed and characterized adenovirus 5 host range mutant (Ad5hr) recombinants encoding HIV(SF162) gp160 (subtype B) and HIV(TV1) gp160 (subtype C). Immunization of mice with one or both induced cellular immunity to subtype B and C peptides by ELISpot, and antibody responses with high binding titers to HIV Env of subtypes A, B, C, and E. Notably, Ad5hr-HIV(TV1) gp160 induced better cellular immunity than Ad5hr-HIV(SF162) gp160, either alone or following co-administration. Thus, the TV1 Env recombinant alone may be sufficient for eliciting immune responses against both subtype B and C envelopes. Further studies of Ad5hr-HIV(TV1) gp160 in rhesus macaques will evaluate the suitability of this insert for a future phase I clinical trial using a replication-competent Ad4 vector.
一种能够引发广泛免疫的 HIV 包膜免疫原对于成功的疫苗至关重要。我们构建并鉴定了编码 HIV(SF162) gp160(B 亚型)和 HIV(TV1) gp160(C 亚型)的腺病毒 5 宿主范围突变(Ad5hr)重组体。用一种或两种免疫原免疫小鼠,通过 ELISpot 检测到针对 B 型和 C 型肽的细胞免疫应答,以及针对 A、B、C 和 E 型 HIV 包膜的高结合滴度的抗体应答。值得注意的是,Ad5hr-HIV(TV1) gp160 诱导的细胞免疫应答优于 Ad5hr-HIV(SF162) gp160,无论是单独使用还是联合使用时。因此,TV1 包膜重组体单独使用可能足以引发针对 B 型和 C 型包膜的免疫应答。进一步在恒河猴中研究 Ad5hr-HIV(TV1) gp160 将评估该插入物在使用复制缺陷型 Ad4 载体进行未来 I 期临床试验中的适用性。