Locher Christopher P, Witt Stephanie A, Ashlock Brittany M, Polacino Patricia, Hu Shiu Lok, Shiboski Stephen, Schmidt Ann M, Agy Michael B, Anderson David M, Staprans Silvija I, zur Megede Jan, Levy Jay A
Department of Medicine, Division of Hematology and Oncology, University of California, 514 Parnassus Avenue, San Francisco, CA 94143-1270, USA.
Vaccine. 2004 Jun 2;22(17-18):2261-72. doi: 10.1016/j.vaccine.2003.11.045.
We determined if the genetic adjuvants, granulocyte-macrophage colony stimulating factor (GM-CSF) and B7-2, could improve the immunogenicity and efficacy of an HIV-2 DNA vaccine. The vaccine consisted of the HIV-2 tat, nef, gag, and env genes synthesized using optimized codons and formulated with cationic liposomes. Baboons (Papio cynocephalus hamadryas) were immunized by the intramuscular, intradermal, and intranasal routes with these expression constructs and challenged with HIV-2(UC2) by the intravaginal route. In the first month after HIV-2 vaginal challenge, the baboons receiving the HIV-2 DNA vaccine with or without the genetic adjuvants had significant reductions in the viral loads in the peripheral blood mononuclear cells (PBMC) (P = 0.028) while the reductions in their plasma viremia were suggestive of a protective effect (P = 0.1). These data demonstrate that partial protection against HIV-2 vaginal challenge, as measured by reduced viral load, can be achieved using only a DNA vaccine formulation.
我们确定了基因佐剂粒细胞-巨噬细胞集落刺激因子(GM-CSF)和B7-2是否能提高HIV-2 DNA疫苗的免疫原性和效力。该疫苗由使用优化密码子合成的HIV-2 tat、nef、gag和env基因组成,并用阳离子脂质体配制。通过肌肉内、皮内和鼻内途径用这些表达构建体免疫狒狒(阿拉伯狒狒),并通过阴道途径用HIV-2(UC2)进行攻击。在HIV-2阴道攻击后的第一个月,接受含或不含基因佐剂的HIV-2 DNA疫苗的狒狒外周血单核细胞(PBMC)中的病毒载量显著降低(P = 0.028),而其血浆病毒血症的降低提示有保护作用(P = 0.1)。这些数据表明,仅使用DNA疫苗制剂就可以实现通过降低病毒载量来衡量的对HIV-2阴道攻击的部分保护。