Hu Duoyi, Bowder Dane, Wei Wenzhong, Thompson Jesse, Wilson Mark A, Xiang Shi-Hua
Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
Vaccine. 2017 May 25;35(23):3067-3075. doi: 10.1016/j.vaccine.2017.04.054. Epub 2017 Apr 29.
The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a striking increase in the immune response due to this stabilized core outer-domain. Therefore, we conclude that the addition of 375W to the outer-domain core of gp120 further stabilizes the structure of immunogen and increases the immunogenicity.
由于其更高的稳定性和免疫原性，gp120的外结构域核心可能比全长gp120更适合作为HIV疫苗免疫原。在我们之前的报告中，我们在gp120的外结构域核心引入了两个二硫键，将其构象固定为与CD4结合的状态，与野生型外结构域核心相比，其免疫原性显著增加。在本报告中，为了进一步提高基于外结构域核心的免疫原的免疫原性，我们在gp120氨基酸序列位置375（375S/W）引入了一个色氨酸残基。我们来自免疫豚鼠的数据确实显示，由于这种稳定的核心外结构域，免疫反应显著增强。因此，我们得出结论，在gp120的外结构域核心添加375W进一步稳定了免疫原的结构并增加了免疫原性。
