Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing 100069, China; Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing 100069, China; Beijing Laboratory of Biomedical Materials, Beijing 100069, China.
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Int J Pharm. 2024 Jul 20;660:124320. doi: 10.1016/j.ijpharm.2024.124320. Epub 2024 Jun 10.
Zika virus (ZIKV) is a mosquito-borne flavivirus that highly susceptibly causes Guillain-Barré syndrome and microcephaly in newborns. Vaccination is one of the most effective measures for preventing infectious diseases. However, there is currently no approved vaccine to prevent ZIKV infection. Here, we developed nanoparticle (NP) vaccines by covalently conjugating self-assembled 24-subunit ferritin to the envelope structural protein subunit of ZIKV to achieve antigen polyaggregation. The immunogenicityof the NP vaccine was evaluated in mice. Compared to monomer vaccines, the NP vaccine achieved effective antigen presentation, promoted the differentiation of follicular T helper cells in lymph nodes, and induced significantly greater antigen-specific humoral and cellular immune responses. Moreover, the NP vaccine enhanced high-affinity antigen-specific IgG antibody levels, increased secretion of the cytokines IL-4 and IFN-γ by splenocytes, significantly activated T/B lymphocytes, and improved the generation of memory T/B cells. In addition, no significant adverse reactions occurred when NP vaccine was combined with adjuvants. Overall, ferritin-based NP vaccines are safe and effective ZIKV vaccine candidates.
寨卡病毒(ZIKV)是一种蚊媒黄病毒,极易导致新生儿格林-巴利综合征和小头畸形。疫苗接种是预防传染病最有效的措施之一。然而,目前尚无预防 ZIKV 感染的批准疫苗。在这里,我们通过将 24 亚基自组装铁蛋白共价偶联到 ZIKV 的包膜结构蛋白亚基上来开发纳米颗粒(NP)疫苗,以实现抗原多聚化。在小鼠中评估了 NP 疫苗的免疫原性。与单体疫苗相比,NP 疫苗实现了有效的抗原呈递,促进了淋巴结滤泡辅助性 T 细胞的分化,并诱导了明显更大的抗原特异性体液和细胞免疫反应。此外,NP 疫苗增强了高亲和力抗原特异性 IgG 抗体水平,增加了脾细胞分泌的细胞因子 IL-4 和 IFN-γ,显著激活了 T/B 淋巴细胞,并改善了记忆 T/B 细胞的生成。此外,NP 疫苗与佐剂联合使用时没有发生明显的不良反应。总的来说,基于铁蛋白的 NP 疫苗是安全有效的寨卡病毒候选疫苗。
Int J Pharm. 2024-7-20
Emerg Microbes Infect. 2018-1-24
Vaccines (Basel). 2024-8-22