Yerkes National Primate Research Center, USA.
J Infect Dis. 2011 Jul 1;204(1):164-73. doi: 10.1093/infdis/jir199.
A simian immunodeficiency virus (SIV) vaccine coexpressing granulocyte-macrophage colony stimulating factor (GM-CSF) prevented infection in 71% of macaques that received 12 rectal challenges. The SIVsmE660 challenge had the tropism of incident human immunodeficiency virus (HIV) infections and a similar genetic distance from the SIV239 vaccine as intraclade HIV isolates. The heterologous prime-boost vaccine regimen used recombinant DNA for priming and recombinant modified vaccinia Ankara for boosting. Co-expression of GM-CSF in the DNA prime enhanced the avidity of elicited immunoglobulin G for SIV envelope glycoproteins, the titers of neutralizing antibody for easy-to-neutralize SIV isolates, and antibody-dependent cellular cytotoxicity. Impressively, the co-expressed GM-CSF increased vaccine-induced prevention of infection from 25% in the non-GM-CSF co-expressing vaccine group to 71% in the GM-CSF co-expressing vaccine group. The prevention of infection showed a strong correlation with the avidity of the elicited Env-specific antibody for the Env of the SIVsmE660 challenge virus (r = 0.9; P < .0001).
一种表达粒细胞-巨噬细胞集落刺激因子（GM-CSF）的猴免疫缺陷病毒（SIV）疫苗可预防 71%接受 12 次直肠挑战的猕猴感染。SIVsmE660 挑战具有与人类免疫缺陷病毒（HIV）感染相同的倾向性，与 SIV239 疫苗的遗传距离与同属内 HIV 分离株相似。使用重组 DNA 进行初始免疫，重组改良安卡拉牛痘病毒（rMVA）进行加强免疫的异源初免-加强疫苗方案。DNA 初免中 GM-CSF 的共表达增强了诱导的免疫球蛋白 G 对 SIV 包膜糖蛋白的亲和力、对易于中和的 SIV 分离株的中和抗体滴度和抗体依赖性细胞毒性。令人印象深刻的是，共表达的 GM-CSF 将疫苗诱导的感染预防率从非 GM-CSF 共表达疫苗组的 25%提高到 GM-CSF 共表达疫苗组的 71%。感染预防率与诱导的 Env 特异性抗体对 SIVsmE660 挑战病毒的 Env 的亲和力呈强相关性（r = 0.9；P <.0001）。
