Induction of long-lasting antibodies and high levels of immune memory using novel alginate-based composite microcapsules--颗粒学报PARTICUOLOGY

Danyang Wang^{a b 1}, Meiyang Yang^{a c 1}, Jingyi Xu^{d 1}, Yuan Gao^{a b}, Haofeng Xia ^e, Jacqueline Fan^f, Yu Lu^g, Peiyan Zhang^h, Shengyu Jiangⁱ, Jing Chen^j, Xueying Yan^c *, Lianyan Wang^{a b *}

a Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China
b University of Chinese Academy of Sciences, Beijing, 100190, China
c Heilongjiang University of Chinese Medicine, Harbin, 150040, China
d National University of Singapore, Singapore, 119077, Singapore
e Fudan University, Shanghai, 200433, China
f Keystone Academy, Beijing, 101318, China
g Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, China
h Beijing 101 High School, Beijing, 100091, China
i Beijing Royal School, Beijing, 102209, China
j Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China

10.1016/j.partic.2026.02.014

Volume 112, May 2026, Pages 52-61

Received 25 September 2025, Revised 22 January 2026, Accepted 13 February 2026, Available online 6 March 2026, Version of Record 17 March 2026.

E-mail: 15159267@qq.com; wanglianyan@ipe.ac.cn

Highlights

• DDAB/PLA NPs were fabricated via nanoprecipitation, Ag@NPs + Ag@NPs-MCs were obtained through spray solidification.

• As a single-shot vaccine, Ag@NPs + Ag@NPs-MCs induced immune responses similar to multiple HBsAg@NPs doses.

• Ag@NPs + Ag@NPs-MCs increased cytokine secretion by splenocytes and improved memory cells 6 months post-immunization.

• Ag@NPs + Ag@NPs-MCs can form antigen-depot at the injection site.

Abstract

The urgent need for single-dose vaccines to combat infectious diseases in resource-limited regions has driven the development of a novel polysaccharide-enhanced delivery platform. In this study, a single-dose vaccine platform has been successfully built, which employed the Hepatitis B surface antigen as the model antigen, and the dimethyl-dioctadecyl-ammonium bromide/poly (lactic acid) (DDAB/PLA) nanoparticles (NPs) as delivery and adjuvant systems. Subsequently, alginate, a biocompatible polysaccharide, was utilized to fabricate composite microcapsules (MCs) via spray-drying, named Ag@NPs + Ag@NPs-MCs, enabling dual antigen delivery: sustained release from alginate-encapsulated Ag@NPs and immediate release of free HBsAg. The mice immunized with the single-dose vaccine induced a sustained increase in antibody levels, promoted cytokines secretion, and greatly improved immune memory T/B cells during the six-month evaluation of sustained immunity. The single-dose vaccine also induced effective short-term immune protection. These immune-boosting effects could be attributed to the vaccine formulations regulating antigen release behavior and the antigen-depot effect at the injection. Therefore, Ag@NPs + Ag@NPs-MCs is a promising platform for a single-dose vaccine against infection.

Graphical abstract

Keywords

Single-dose vaccine; Antigen-depot effect; Immune response

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