Precision Wormlike Nanoadjuvant Governs Potency of Vaccination
- Ziyang Sun
Ziyang SunSchool of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, ChinaMore by Ziyang Sun
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- Dongdong Qiao
Dongdong QiaoSchool of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, ChinaMore by Dongdong Qiao
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- Yi Shi
Yi ShiSchool of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, ChinaMore by Yi Shi
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- Matthias Barz
Matthias BarzLeiden Academic Center for Drug Research, Division of Biotherapeutics, Laboratory for Biotherapeutic Delivery, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsDepartment Chemie, Johannes Gutenberg University, Duesbergweg 10-14, 55099 Mainz, GermanyMore by Matthias Barz
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- Lixin Liu*
Lixin Liu*Email: [email protected]School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaMore by Lixin Liu
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- Yongming Chen*
Yongming Chen*Email: [email protected]School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaMore by Yongming Chen
Abstract
It remains unclear how the precise length of one-dimensional nanovehicles influences the characters of vaccination. Here, a unimolecular nanovehicle with tailored size and aspect ratio (AR) is applied to deliver CpG oligodeoxynucleotide, a Toll-like receptor (TLR) 9 agonist, as an adjuvant of recombinant hepatitis B virus surface antigen (rHBsAg), for treating chronic hepatitis B (CHB). Cationic nanovehicles with fixed width (ca. 45 nm) but varied length (46 nm–180 nm), AR from 1 to 4, are prepared through controlled polymerization and are loaded with CpG by electrostatic interaction. We reveal that the nanoadjuvant with AR = 2 shows the highest retention in proximal lymph nodes. Importantly, it is more easily internalized into antigen-presenting cells and accumulates in the late endosome, where TLR9 is located. Such a nanoadjuvant exhibits the strongest immune response with rHBsAg to clear the hepatitis B virus in the CHB mouse model, showing that the AR of nanovehicles governs the efficiency of vaccination.
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