Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD, USA.
Vaccine. 2012 Jan 5;30(2):336-41. doi: 10.1016/j.vaccine.2011.10.085. Epub 2011 Nov 12.
A prototype dengue-1 DNA vaccine was shown to be safe and immunogenic in a previous Phase 1 clinical trial. Anti-dengue-1 neutralizing antibody responses were detectable only in the group of volunteers receiving the high dose of nonadjuvanted vaccine and the antibody titers were low. Vaxfectin(®), a lipid-based adjuvant, enhances the immunogenicity of DNA vaccines. We conducted a nonhuman primate study to evaluate the effect of Vaxfectin(®) on the immunogenicity of a tetravalent dengue DNA vaccine. Animals were immunized on days 0, 28 and 84, with each immunization consisting of 3mg of Vaxfectin(®)-adjuvanted tetravalent dengue DNA vaccine. The use of Vaxfectin(®) resulted in a significant increase in anti-dengue neutralizing antibody responses against dengue-1, -3 and -4. There was little to no effect on T cell responses as measured by interferon gamma ELISPOT assay. Animals immunized with the Vaxfectin(®)-formulated tetravalent DNA vaccine showed significant protection against live dengue-2 virus challenge compared to control animals (0.75 mean days of viremia vs 3.3 days). Animals vaccinated with nonadjuvanted DNA had a mean 2.0 days of viremia. These results support further evaluation of the Vaxfectin(®)-adjuvanted tetravalent dengue DNA vaccine in a Phase 1 clinical trial.
一种登革热 1 型 DNA 疫苗的原型在之前的 1 期临床试验中被证明是安全和免疫原性的。只有在接受高剂量非佐剂疫苗的志愿者组中才能检测到抗登革热 1 型中和抗体反应，且抗体滴度较低。Vaxfectin(®)是一种基于脂质的佐剂，可增强 DNA 疫苗的免疫原性。我们进行了一项非人类灵长类动物研究，以评估 Vaxfectin(®)对四价登革热 DNA 疫苗免疫原性的影响。动物在第 0、28 和 84 天进行免疫接种，每次免疫接种由 3mg Vaxfectin(®)佐剂的四价登革热 DNA 疫苗组成。使用 Vaxfectin(®)可显著增加针对登革热 1、3 和 4 的中和抗体反应。干扰素γ ELISPOT 测定法测量的 T 细胞反应几乎没有影响。与对照动物相比，用 Vaxfectin(®)配制的四价 DNA 疫苗免疫的动物对活的登革热 2 型病毒攻击表现出显著的保护作用（平均病毒血症期为 0.75 天 vs. 3.3 天）。用非佐剂 DNA 疫苗接种的动物的平均病毒血症期为 2.0 天。这些结果支持在 1 期临床试验中进一步评估 Vaxfectin(®)佐剂的四价登革热 DNA 疫苗。
