Development of novel cationic microemulsion as parenteral adjuvant for influenza vaccine

• 作者: Angkana Tantituvanont Garnpimol Ritthidej Sakalanunt Lamaisakul Vimolmas Lipipun
• 来源期刊: 亚洲药物制剂科学(英文)
• 学科: 化学
• 关键词: Cationic microemulsion ADJUVANT Influenza virus VACCINE
• 年，卷（期）: 2020,（5）
• 页码范围: 591-604
• 页数: 14页
• 分类号: O64

摘要

Squalene-based oil-in-water(O/W)emulsions have been used as effective and safe adjuvants in approved influenza vaccines.However,there are concerns regarding the safety and side effects of increasing risk of narcolepsy.In present study,novel O/W microemulsions(MEs)containing wheat germ oil,D-alpha tocopheryl polyethylene glycol 1000 succinate(TPGS)and Cremophor EL(CreEL)or Solutol HS15 were formulated with/without a cationic surfactant,cetyltrimethylammonium bromide(CTAB)and then sterilized by autoclaving.Their physical properties and biological efficacies were evaluated.The results demonstrated that autoclaving reduced the droplet size to~20 nm with narrow size distributions resulting in monodisperse systems with good stability up to 3 years.Hemolytic activity,viscosity,pH,and osmolality were appropriate for parenteral use.Bovine serum albumin(BSA),a model antigen,after mixing with MEs retained the protein integrity,assessed by SDS-PAGE and CD spectroscopy.Greater percentages of 28 SC cell viability were observed from CreEL-based MEs.Uptake of FITC-BSA-MEs increased with the increasing concentration of CTAB confirmed by CLSM images.Furthermore,cationic CreEL-based MEs could induce Th1 cytokine synthesis with an increase in TNF-α and IL-12 levels and a decrease in IL-10 level.In vivo immunization study in mice of adjuvants admixed with influenza virus solution revealed that nonionic and selected cationic CreEL-MEs enhanced immune responses as measured by influenza-specific serum antibody titers and hemagglutination inhibition titers.Particularly,cationic CreEL-based ME showed better humoral and cellular immunity with higher IgG2 a titer than nonionic CreEL-based ME and antigen alone.No differences in immune responses were observed between mice immunized with selected cationic CreEL-based ME and marketed adjuvant.In addition,the selected ME induced antigen-sparing while retained immune stimulating effects compared to antigen alone.No inflammatory change in muscle fiber structure was observed.Accordingly,the develo