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A Novel Human Papillomavirus 16 L1 Pentamer-Loaded Hybrid Particles Vaccine System: Influence of Size on Immune Responses
Jia, Chengcheng1,2; Yang, Tingyuan1; Liu, Yongjiang2; Zhu, Ali1; Yin, Fei2; Wang, Yajun2; Xu, Lan2; Wang, Yan2; Yan, Mei2; Cai, Qingman3; Liang, Xiaoxu3; Ju, Ruijun3; Chen, Jianping2; Wang, Lianyan1
2018-10-24
发表期刊ACS APPLIED MATERIALS & INTERFACES
ISSN1944-8244
卷号10期号:42页码:35745-35759
摘要Cervical cancer remains the second-most prevalent female malignancy around the world, leading to a great majority of cancer-related mortality that occurs mainly in developing countries. Developing an effective and low-cost vaccine against human papillomavirus (HPV) infection, especially in medically underfunded areas, is urgent. Compared with vaccines based on HPV L1 viruslike particles (VLPs) in the market, recombinant HPV L1 pentamer expressed in Escherichia coli represents a promising and potentially cost-effective vaccine for preventing HPV infection. Hybrid particles comprising a polymer core and lipid shell have shown great potential compared to conventional aluminum salts adjuvant and is urgently needed for HPV L1 pentamer vaccines. It is well-reported that particle sizes are crucial in regulating immune responses. Nevertheless, reports on the relationship between the particulate size and the resultant immune response have been in conflict, and there is no answer to how the size of particles regulates specific immune response for HPV L1 pentamer-based candidate vaccines. Here, we fabricated HPV 16 L1 pentamer-loaded poly(D,L-lactide-co-glycolide) (PLGA)/lecithin hybrid particles with uniform sizes (0.3, 1, and 3 mu m) and investigated the particle size effects on antigen release, activation of lymphocytes, dendritic cells (DCs) activation and maturation, follicular helper CD4(+) T (TFH) cells differentiation, and release of pro-inflammatory cytokines and chemokines. Compared with the other particle sizes, 1 mu m particles induced more powerful antibody protection and yielded more persistent antibody responses, as well as more heightened anamnestic responses upon repeat vaccination. The superior immune responses might be attributed to sustainable antigen release and robust antigen uptake and transport and then further promoted a series of cascade reactions, including enhanced DCs maturation, increased lymphocytes activation, and augmented TFH cells differentiation in draining lymph nodes (DLNs). Here, a powerful and economical platform for HPV vaccine and a comprehensive understanding of particle size effect on immune responses for HPV L1 pentamer-based candidate vaccines are provided.
关键词human papillomavirus pentamer particle size adjuvant
DOI10.1021/acsami.8b11556
语种英语
关键词[WOS]LIPID-POLYMER HYBRID ; IN-VITRO MODEL ; DRUG-DELIVERY ; ANTIGEN RELEASE ; T-CELLS ; BIODEGRADABLE NANOPARTICLES ; DEVELOPING-COUNTRIES ; ESCHERICHIA-COLI ; DENDRITIC CELLS ; SURFACE-CHARGE
资助项目National Science and Technology Major Project of China[2016ZX10004001-005] ; National Science and Technology Major Project of China[2014ZX09102045-008] ; National Science Foundation of China[21476243] ; Special Innovation Fund for Beijing Economic-Technological Development Area[JSYF2012658]
WOS研究方向Science & Technology - Other Topics ; Materials Science
WOS类目Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
项目资助者National Science and Technology Major Project of China ; National Science Foundation of China ; Special Innovation Fund for Beijing Economic-Technological Development Area
WOS记录号WOS:000448754500009
出版者AMER CHEMICAL SOC
引用统计
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/26471
专题中国科学院过程工程研究所
通讯作者Chen, Jianping; Wang, Lianyan
作者单位1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Beijing Hlth Guard Biotechnol Co LTD, Beijing 100176, Peoples R China
3.Beijing Inst Petrochem Technol, Beijing 102617, Peoples R China
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GB/T 7714
Jia, Chengcheng,Yang, Tingyuan,Liu, Yongjiang,et al. A Novel Human Papillomavirus 16 L1 Pentamer-Loaded Hybrid Particles Vaccine System: Influence of Size on Immune Responses[J]. ACS APPLIED MATERIALS & INTERFACES,2018,10(42):35745-35759.
APA Jia, Chengcheng.,Yang, Tingyuan.,Liu, Yongjiang.,Zhu, Ali.,Yin, Fei.,...&Wang, Lianyan.(2018).A Novel Human Papillomavirus 16 L1 Pentamer-Loaded Hybrid Particles Vaccine System: Influence of Size on Immune Responses.ACS APPLIED MATERIALS & INTERFACES,10(42),35745-35759.
MLA Jia, Chengcheng,et al."A Novel Human Papillomavirus 16 L1 Pentamer-Loaded Hybrid Particles Vaccine System: Influence of Size on Immune Responses".ACS APPLIED MATERIALS & INTERFACES 10.42(2018):35745-35759.
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