A Single-dose Vaccine Using Ultrasound-responsive Hydrogel for Controlled Antigen Release and Enhanced Immunization Efficacy

Zhi-Yuan Shi; Xing-Hui Si; Ren-Ming Wan; Zhen-Yi Zhu; Wan-Tong Song; Xue-Si Chen

doi:10.1007/s10118-025-3397-4

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A Single-dose Vaccine Using Ultrasound-responsive Hydrogel for Controlled Antigen Release and Enhanced Immunization Efficacy

RESEARCH ARTICLE | Updated：2025-09-26

- A Single-dose Vaccine Using Ultrasound-responsive Hydrogel for Controlled Antigen Release and Enhanced Immunization Efficacy
- A Single-dose Vaccine Using Ultrasound-responsive Hydrogel for Controlled Antigen Release and Enhanced Immunization Efficacy
- 高分子科学（英文） 2025年43卷第10期页码：1814-1824
- Affiliations：
  
  a.School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
  b.State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
  c.Harbin Institute of Technology Zhengzhou Research Institute Medical Health Research Institute, Zhengzhou 450000, China
- Author bio：
  
  sixinghui@hitzri.cn (X.H.S.)
  wtsong@ciac.ac.cn (W.T.S.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. W2412020 and 22222509), China Science and Technology Exchange Center Joint Project on Vaccine Research and Development (No. 2024VTJP1004), Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers (No. YDZJ202402077CXJD).;Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-025-3397-4.
- DOI：10.1007/s10118-025-3397-4
  中图分类号：
- 收稿：2025-05-16，
  
  修回：2025-06-12，
  
  录用：2025-06-15，
  
  网络首发：2025-09-02，
  
  纸质出版：2025-10-05
- Accepted：
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Shi, Z. Y.; Si, X. H.; Wan, R. M.; Zhu, Z. Y.; Song, W. T.; Chen, X. S. A single-dose vaccine using ultrasound-responsive hydrogel for controlled antigen release and enhanced immunization efficacy. Chinese J. Polym. Sci. 2025, 43, 1814–1824

Zhi-Yuan Shi, Xing-Hui Si, Ren-Ming Wan, et al. A Single-dose Vaccine Using Ultrasound-responsive Hydrogel for Controlled Antigen Release and Enhanced Immunization Efficacy[J]. Chinese Journal of Polymer Science, 2025, 43(10): 1814-1824.
Shi, Z. Y.; Si, X. H.; Wan, R. M.; Zhu, Z. Y.; Song, W. T.; Chen, X. S. A single-dose vaccine using ultrasound-responsive hydrogel for controlled antigen release and enhanced immunization efficacy. Chinese J. Polym. Sci. 2025, 43, 1814–1824 DOI： 10.1007/s10118-025-3397-4.

Zhi-Yuan Shi, Xing-Hui Si, Ren-Ming Wan, et al. A Single-dose Vaccine Using Ultrasound-responsive Hydrogel for Controlled Antigen Release and Enhanced Immunization Efficacy[J]. Chinese Journal of Polymer Science, 2025, 43(10): 1814-1824. DOI： 10.1007/s10118-025-3397-4.

摘要

In order to achieve controlled multiple boosts of antigen release

we mix

ed 4-arm PEG-Se-Se-ONH

ODEX and 4-arm PEG-ONH

to prepare ultrasound-responsive hydrogel (URH) and successfully realized ultrasonic responsive release. URH is capable of sustaining antigen release under physiological conditions and can further boost antigen release upon ultrasound triggering. Due to the optimization of the release mode

the level of humoral immunity was highly enhanced.

Abstract

Sustained antigen release from delivery systems is a pivotal strategy to enhance vaccine-induced immune responses

primarily by mimicking the antigen exposure kinetics of natural infections to synchronously boost humoral and cellular immunity. However

the absence of an "antigen boost" effect in current approaches stands as a critical bottleneck

limiting the intensity and durability of immune responses. To address the critical gap of insufficient antigen boosting in sustained-release vaccine platforms

we engineered an ultrasound-responsive hydrogel (URH) with diselenide-functionalized 4-arm PEG-ONH

(4-arm PEG-Se-Se-ONH

)

4-arm PEG-ONH

and ODEX. Leveraging its exceptional ultrasonic sensitivity

the URH enables timely controlled

multiple-boost antigen release both

in vitro

and

in vivo

overcoming the limitations of conventional sustained-release systems. With the multiple boost release mode triggered by ultrasound

the immune response in lymph nodes was significantly stronger than that in sustained release group without ultrasonic trigger. At the same time

it also greatly improved the humoral immunity level

URH+US-OVA elicited 7.5×10

-fold higher anti-OVA Ig

titers over commercial Al-OVA vaccines and 440-fold higher than URH-OVA vaccines at day 40 post-vaccination

while the levels of blood routine and inflammatory factors were within the normal range

which proved that the safety of URH vaccines. The results support that the antigen release mode is a key factor affecting the immunological efficacy of vaccines

and URH can be modularized to regulate the multiple boost antigen release mode.

关键词

Keywords

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