Enhanced Cellular Immunity for Hepatitis B Virus Vaccine: A Novel Polyinosinic-Polycytidylic Acid-Incorporated Adjuvant Leveraging Cytoplasmic Retinoic Acid-Inducible Gene-Like Receptor Activation and Increased Antigen Uptake
Source abstract
Abstract
Conventional aluminum adjuvants exhibit limited cellular immunity. Polyinosinic-polycytidylic acid (poly I:C) activates cytoplasmic retinoic acid-inducible gene-like receptor (RLR), triggering strong T cell activation and cellular responses. However, when applied as an adjuvant, its limited endocytosis and restricted cytoplasmic delivery diminish its effectiveness and increase its toxicity. Hybrid polymer–lipid nanoparticle (PLNP) possesses numerous benefits such as good stability, reduced drug leakage, simple fabrication, easy property modulation, and excellent reproducibility compared to the lipid nanoparticle or the polymeric vector. Here, we developed a novel cationic polymer–lipid hybrid adjuvant capable of incorporating poly I:C to enhance cellular immunity. The hepatitis B surface antigen (HBsAg) was immobilized onto poly I:C-incorprated PLNP (PPLNP) via electrostatic interactions, forming the HBsAg/PPLNP vaccine formulation. The PPLNP adjuvant largely enhanced the cellular endocytosis and cytoplasmic transport of poly I:C, activating RLR followed by promoting type I interferon (IFN) secretion. Meanwhile, PPLNP obviously enhanced the antigen uptake, prolonged antigen retention at the site of administration, and facilitated enhanced transport of antigens to lymph nodes. The HBsAg/PPLNP nanovaccine led to amplified concentrations of antigen-specific immunoglobulin G (IgG), IFN-γ, granzyme B, and an enhanced IgG2a/IgG1 ratio, alongside the FasL + /CD8 + T cell activation, favoring a T helper 1 (T H 1)-driven immune response. PPLNP, distinguished by its biocompatibility, ease of fabrication, and effectiveness in augmenting cellular immunity, holds significant promise as a new adjuvant.
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Research context
OpenAlex topics: Hepatitis B Virus Studies · Immunotherapy and Immune Responses · interferon and immune responses
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Institute for Inheritance-Based Innovation of Chinese Medicine, Marshall Laboratory of Biomedical Engineering, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.
Department of Pharmacy, First People’s Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, 650034 Yunnan, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Research Institute for Biomaterials, Tech Institute for Advanced Materials, Bioinspired Biomedical Materials & Devices Center, College of Materials Science and Engineering, Jiangsu Collaborative Innovation Center for Advanced Inorganic Function Composites, Suqian Advanced Materials Industry Technology Innovation Center, Nanjing Tech University, Nanjing 211816 China.
Funding
Basic and Applied Basic Research Foundation of Guangdong Province · Shenzhen High-end Talent Scientific Research Start-up Foundation · National Natural Science Foundation of China · Research Project of the First People’s Hospital of Yunnan Province · Jiangsu Distinguished Professor Program · Research Project of the Clinical Pharmacy Center of Yunnan Province
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