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首页> 外文期刊>Vaccine >Broad HIV-1 neutralizing antibody response induced by heterologous gp140/gp145 DNA prime-vaccinia boost immunization.
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Broad HIV-1 neutralizing antibody response induced by heterologous gp140/gp145 DNA prime-vaccinia boost immunization.

机译：异源gp140 / gp145 DNA初免疫苗诱导免疫诱导的广泛HIV-1中和抗体应答。

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Objective: To develop an effective HIV vaccine strategy that can induce cross-reactive neutralizing antibody. Methods: Codon-optimized gp140 and gp145 env genes derived from HIV-1cn54, 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- gamma 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. Results: 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. Conclusions: This heterologous prime-boost immunization strategy could be used to design immunogen-generating broad neutralizing antibodies against genetic variance pathogens.Digital Object Identifier http://dx.doi.org/10.1016/j.vaccine.2012.04.075
机译：目的：制定一种可诱导交叉反应中和抗体的有效HIV疫苗策略。方法：构建由CRF07 B'/ C重组株HIV-1 cn54 获得的经密码子优化的gp140和gp145 env基因，作为DNA疫苗和重组天坛牛痘疫苗。在小鼠和豚鼠中测试了用gp140和gp145进行异源免疫的效果。使用IFN-γELISPOT分析检测T细胞反应。使用一组进化枝B'和B'/ C HIV-1和TZM-bl细胞的主要分离物来确定免疫血清的中和活性。结果：异源免疫原免疫诱导的中和抗体（NAbs）中了豚鼠模型中的所有HIV-1 B'和B'/ C主要分离株。在最后一次接种后6周，Gp145和gp140异源初免-增强诱导了最佳的中和抗体反应，具有宽广的中和谱，最高滴度为1：270。但是，T细胞对HIV-1肽的反应明显弱于gp145 + gp145同源初免-增强。结论：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免疫原的广泛中和抗体。数字对象标识符http://dx.doi.org/10.1016/j.vaccine.2012.04.075

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