免疫原性
类病毒颗粒
抗原
乙型肝炎表面抗原
免疫系统
化学
病毒学
生物
病毒
乙型肝炎病毒
免疫学
生物化学
重组DNA
基因
作者
Min Li,Zhihui Liang,Chen Chen,Guang Yu,Zhiying Yao,Yiyang Guo,Lei Zhang,Hang Bao,Duo Fu,Xuecheng Yang,Huiyang Wang,Changying Xue,Bingbing Sun
出处
期刊:ACS Nano
[American Chemical Society]
日期:2022-06-28
卷期号:16 (7): 10482-10495
被引量:15
标识
DOI:10.1021/acsnano.2c01283
摘要
Virus-like particles (VLPs) are self-assembled viral proteins that represent a superior form of antigens in vaccine formulations. To enhance immunogenicity, adjuvants, especially the aluminum salts (Alum), are essentially formulated in VLP vaccines. However, Alum only induce biased humoral immune responses that limits further applications of VLP-based vaccines. To stimulate more balanced immunity, we, herein, develop a one-step strategy of using VLPs as the biotemplates to synthesize raspberry-like silica-adjuvanted VLP@Silica nanovaccines. Hepatitis B surface antigen (HBsAg) VLPs and human papillomavirus type 18 (HPV 18) VLPs are selected as model templates. Circular dichroism (CD) and affinity analyses demonstrate that HBsAg VLPs in the nanovaccines maintain their secondary structure and immunogenicity, respectively. VLP@Silica promote silica dissolution-induced lysosomal escape and cytosolic delivery of antigens, and enhance the secretion of both Th1 and Th2 type cytokines in murine bone marrow-derived dendritic cells (BMDCs). Additionally, they could improve antigen trafficking and mediate DC activation in draining lymph nodes (DLNs). Vaccination study demonstrate that both HBsAg VLP@Silica and HPV 18 VLP@Silica nanovaccines induce enhanced antigen-specific antibody productions and T-cell mediated adaptive immune responses. This design strategy can utilize VLPs derived from a diversity of viruses or their variants as templates to construct both prophylactic and therapeutic vaccines with improved immunogenicity.
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