Xu Ziyang, Chokkalingam Neethu, Tello-Ruiz Edgar, Walker Susanne, Kulp Daniel W, Weiner David B
The Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA.
iScience. 2020 Aug 21;23(8):101399. doi: 10.1016/j.isci.2020.101399. Epub 2020 Aug 6.
CD4+ T cells play an important role in the maturation of the antibody responses. Conjugation of identified CD4+ T cell helper epitope to the target antigen has been developed as a strategy to enhance vaccine-induced humoral immunity. In this work, we reported the identification of a novel HLA-IAb helper epitope LS-3 from Aquifex aeolicus. In silico analysis predicted this epitope to have high binding affinity to common human HLA alleles and have complementary binding coverage to the established PADRE epitope. Introduction of HLA-IAb knockout mutations to the LS-3 epitope significantly attenuated humoral responses induced by a vaccine containing this epitope. Finally, engineered fusion of the epitope to a model antigen, influenza hemagglutinin, significantly improved both binding and hemagglutination inhibition antibody responses in mice receiving DNA or protein vaccines. In summary, LS-3 and additional identified CD4+ helper epitopes may be further explored to improve vaccine responses in translational studies.
CD4+ T细胞在抗体应答的成熟过程中发挥着重要作用。将已鉴定的CD4+ T细胞辅助表位与靶抗原偶联，已被开发为一种增强疫苗诱导的体液免疫的策略。在这项工作中，我们报告了从嗜热栖热菌中鉴定出一种新的HLA-IAb辅助表位LS-3。计算机分析预测该表位对常见人类HLA等位基因具有高结合亲和力，并且与已确立的PADRE表位具有互补的结合覆盖范围。对LS-3表位引入HLA-IAb敲除突变显著减弱了含有该表位的疫苗诱导的体液应答。最后，将该表位与模型抗原流感血凝素进行工程融合，显著改善了接受DNA或蛋白质疫苗的小鼠的结合和血凝抑制抗体应答。总之，在转化研究中，可能需要进一步探索LS-3和其他已鉴定的CD4+辅助表位，以改善疫苗应答。
