State Key Laboratory for Infectious Diseases Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China.
Vaccine. 2012 Jun 13;30(28):4135-43. doi: 10.1016/j.vaccine.2012.04.075. Epub 2012 May 2.
To develop an effective HIV vaccine strategy that can induce cross-reactive neutralizing antibody.
Codon-optimized gp140 and gp145 env genes derived from HIV-1(cn54), a CRF07 B'/C recombinant strain, were constructed as DNA and recombinant Tiantan vaccinia (rTV) vaccines. The effect of heterologous immunization with gp140 and gp145 was tested in mice and guinea pigs. T cell responses were detected using the IFN-γ ELISPOT assay. A panel of primary isolates of clade B' and B'/C HIV-1 and TZM-bl cells was used to determine the neutralizing activity of immunized sera.
The neutralizing antibodies (NAbs) induced by the heterologous immunogen immunization neutralized all HIV-1 B' and B'/C primary isolates in the guinea pig model. Gp145 and gp140 heterologous prime-boost induced the best neutralizing antibody response with a broad neutralizing spectrum and the highest titer of 1:270 at 6 weeks after the last inoculation. However, the T cell response to HIV-1 peptides was significantly weaker than the gp145+gp145 homologous prime-boost.
This heterologous prime-boost immunization strategy could be used to design immunogen-generating broad neutralizing antibodies against genetic variance pathogens.
开发一种能够诱导交叉反应性中和抗体的有效 HIV 疫苗策略。
构建了源自 HIV-1(cn54)（一种 CRF07 B'/C 重组株）的经过密码子优化的 gp140 和 gp145 env 基因的 DNA 和重组天坛痘苗（rTV）疫苗。在小鼠和豚鼠中测试了 gp140 和 gp145 异源免疫的效果。使用 IFN-γ ELISPOT 测定法检测 T 细胞反应。使用一组 B'和 B'/C HIV-1 组的主要分离株和 TZM-bl 细胞来确定免疫血清的中和活性。
异源免疫原免疫诱导的中和抗体（NAbs）中和了豚鼠模型中所有的 HIV-1 B'和 B'/C 主要分离株。gp145 和 gp140 异源初免-加强诱导的中和抗体反应最佳，具有广泛的中和谱，最后一次接种后 6 周时的效价最高为 1:270。然而，HIV-1 肽的 T 细胞反应明显弱于 gp145+gp145 同源初免-加强。
这种异源初免-加强免疫策略可用于设计针对遗传变异病原体的产生广谱中和抗体的免疫原。
