Co-delivery of antigen and dual adjuvants by aluminum hydroxide nanoparticles for enhanced immune responses
| Autor: | Zixuan Zhou, Tao Gong, Ying Wang, Ling Zhang, Lu Tan, Y.P. Hou, Yao Tang, Xun Sun |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Ovalbumin
CpG Oligodeoxynucleotide medicine.medical_treatment Pharmaceutical Science Aluminum Hydroxide 02 engineering and technology Mice 03 medical and health sciences Immune system Adjuvants Immunologic Antigen medicine Animals Cytotoxic T cell Antigens 030304 developmental biology 0303 health sciences biology Chemistry Pattern recognition receptor 021001 nanoscience & nanotechnology Cell biology Mice Inbred C57BL Oligodeoxyribonucleotides Humoral immunity biology.protein Nanoparticles 0210 nano-technology Adjuvant |
| Zdroj: | Journal of Controlled Release. 326:120-130 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2020.06.021 |
| Popis: | Adjuvants that contain pathogen-associated molecular patterns (PAMPs) can enhance vaccination efficacy by binding to pattern recognition receptors (PRRs), thereby stimulating immune responses. Particularly effective may be the combination of multiple PAMPs that activate different PRRs, which occurs with natural pathogens. Here we hypothesized the enhanced effects would occur in two adjuvants that stimulate different PRRs: CpG oligodeoxynucleotide (CpG-ODN), which is Toll-like receptor 9 agonist; and 5′-triphosphate, short, double-stranded RNA (3pRNA), which activates retinoic acid-inducible gene I (RIG-I). The model antigen ovalbumin (OVA) was loaded and adjuvants were surface-adsorbed to aluminum hydroxide nanoparticles (hereafter NP-3pRNA-CpG) by electrostatic interaction with an average size of 120 nm and a negative surface charge for targeting lymph nodes. These nanoparticles were efficiently internalized by antigen-presenting cells (APCs) in the lymph nodes, and the resulting APC activation and antigen cross-presentation generated strong humoral immunity and cytotoxic T lymphocyte responses and IFN-γ secretion. NP-3pRNA-CpG significantly suppressed B16-OVA tumor growth and prolonged survival of tumor-bearing mice in therapeutic and prophylactic models, illustrating the enhanced effects of CpG-ODN and 3pRNA. Our study highlights the potential of combining multiple adjuvants for effective vaccine design. |
| Databáze: | OpenAIRE |
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