Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine

Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine.

登革病毒（Dengue virus, DENV）是全球范围内的重大公共卫生威胁。预防登革热的核心防护环节为中和抗体应答。从登革病毒2型（DENV-2）感染的人血清中纯化的抗登革病毒免疫球蛋白G（IgG），经酶联免疫吸附试验（Enzyme-Linked Immunosorbent Assay, ELISA）与表位提取技术检测时，可与多种肽段发生特异性反应。研究采用多步骤计算方法，预测了登革病毒2型E蛋白上的6个抗原区域，该结果与联合ELISA及表位提取方法所鉴定的6个表位完全吻合。将代表B细胞表位的筛选肽段与已知的登革病毒T辅助表位（T-helper epitope）结合后，对其疫苗效力开展评估。小鼠免疫实验结果显示，两种新型合成疫苗构建体可诱导良好的体液免疫应答，并产生针对登革病毒1型、2型及3型的交叉反应性中和抗体。本研究成果为表位作图研究提供了新方向，同时为基于多表位的合成肽疫苗的后续开发奠定了理论基础。