Chan Yanqi, Jazayeri Seyed Davoud, Ramanathan Babu, Poh Chit Laa
Centre for Virus and Vaccine Research, School of Science and Technology, Sunway University, Subang Jaya 47500, Malaysia.
Department of Biological Sciences, School of Science and Technology, Sunway University, Subang Jaya 47500, Malaysia.
Vaccines (Basel). 2020 Jul 25;8(3):417. doi: 10.3390/vaccines8030417.
Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1-P4) were designed by linking a universal T-helper epitope (PADRE or TpD) to the highly conserved CD8 T cell epitope and B cell epitope (B1 or B2) against all four DENV serotypes. The multi-epitope peptides were conjugated to polystyrene nanoparticles (PSNPs) and four nanovaccines (NP1-NP4) were constructed. Mice immunized with NP1-NP4 elicited significantly higher titers of IgG and neutralizing antibodies when compared to immunization with naked P1-P4. The immune responses in mice immunized with peptide vaccines were compared with nanovaccines using ELISA, ELISPOT, and a neutralization test based on FRNT. Among the four conjugated peptide nanovaccines, NP3 comprising the TpD T-helper epitope linked to the highly conserved B1 epitope derived from the E protein was able to elicit significant levels of IFN-γ and neutralizing antibodies to all four dengue serotypes. NP3 is a promising tetravalent synthetic peptide vaccine, but the selection of a more effective CD8 T cell epitope and adjuvants to further improve the immunogenicity is warranted.
疫苗接种仍然是预防登革热的主要方法。由于唯一获得许可的减毒活疫苗（LAV）对所有四种血清型均缺乏效力，因此应探索其他疫苗平台，如合成肽疫苗。在本研究中，通过将通用T辅助表位（PADRE或TpD）与针对所有四种登革病毒血清型的高度保守的CD8 T细胞表位和B细胞表位（B1或B2）连接，设计了四种多表位肽（P1-P4）。将多表位肽与聚苯乙烯纳米颗粒（PSNP）偶联，构建了四种纳米疫苗（NP1-NP4）。与用裸露的P1-P4免疫相比，用NP1-NP4免疫的小鼠产生的IgG和中和抗体滴度显著更高。使用ELISA、ELISPOT和基于FRNT的中和试验，比较了用肽疫苗免疫的小鼠与纳米疫苗的免疫反应。在四种偶联肽纳米疫苗中，包含与源自E蛋白的高度保守B1表位连接的TpD T辅助表位的NP3能够引发针对所有四种登革热血清型的显著水平的IFN-γ和中和抗体。NP3是一种有前景的四价合成肽疫苗，但需要选择更有效的CD8 T细胞表位和佐剂以进一步提高免疫原性。
