Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States.
Vaccine. 2012 Jan 11;30(3):506-9. doi: 10.1016/j.vaccine.2011.11.079. Epub 2011 Nov 29.
The global sequence diversity of HIV-1 presents a daunting challenge for vaccine development. We investigated whether a heterologous insert prime-boost regimen could expand global coverage by selectively boosting cellular immune responses to conserved epitopes. Rhesus monkeys were primed and boosted with recombinant adenovirus vectors expressing homologous or heterologous HIV-1 Gag sequences that were optimized to focus responses on highly conserved epitopes. We observed comparable responses directed to specific regions of the Gag protein in all experimental groups without evidence of improved coverage or expanded breadth in the heterologous insert group. These data suggest that antigen-independent factors contribute to the immunodominance patterns of vaccine-elicited cellular immune responses.
HIV-1 的全球序列多样性对疫苗开发构成了巨大挑战。我们研究了异源插入物的初免-加强免疫方案是否可以通过选择性增强对保守表位的细胞免疫反应来扩大全球覆盖范围。恒河猴用表达经优化以聚焦于高度保守表位的同源或异源 HIV-1 Gag 序列的重组腺病毒载体进行初免和加强免疫。我们观察到所有实验组对 Gag 蛋白特定区域的反应相当,没有证据表明异源插入组的覆盖范围或广度得到改善。这些数据表明,抗原非依赖性因素有助于疫苗诱导的细胞免疫反应的免疫优势模式。