Effective and Safe Stimulation of Humoral and Cell-Mediated Immunity by Intradermal Immunization with a Cyclic Dinucleotide/Nanoparticle Combination Adjuvant
| Autor: | Jackeline Franco, Yung-Yi C. Mosley, Juan F Hernandez-Franco, Harm HogenEsch, Darryl Ragland, Yuan Yao |
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| Rok vydání: | 2021 |
| Předmět: |
Injections
Intradermal Swine medicine.medical_treatment Immunology Population Spleen Mice Immune system Adjuvants Immunologic Cyclic AMP medicine Animals Humans Immunology and Allergy education Lymph node Cells Cultured Immunity Cellular Mice Inbred BALB C education.field_of_study business.industry NF-kappa B Germinal center Dendritic Cells Dendritic cell Plants Th1 Cells Immunity Humoral medicine.anatomical_structure Immunization Nanoparticles Female Inflammation Mediators business Adjuvant Signal Transduction |
| Zdroj: | The Journal of Immunology. 206:700-711 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Intradermal (ID) immunization is an attractive route of vaccination because it targets tissue rich in dendritic cells, has dose-sparing potential, and allows needle-free delivery. However, few adjuvants are effective, nonreactogenic, and compatible with needle-free delivery devices. In this study, we demonstrate that a combination adjuvant composed of cyclic-di-AMP (cdAMP) and the plant-derived nanoparticle adjuvant Nano-11 significantly enhanced the immune response to ID-injected vaccines in mice and pigs with minimal local reaction at the injection site. The cdAMP/Nano-11 combination adjuvant increased Ag uptake by lymph node–resident and migratory skin dendritic cell subpopulations, including Langerhans cells. ID immunization with cdAMP/Nano-11 expanded the population of germinal center B cells and follicular helper T cells in the draining lymph node and Ag-specific Th1 and Th17 cells in the spleen. It elicited an enhanced immune response with a significant increase of IgG1 and IgG2a responses in mice at a reduced dose compared with i.m. immunization. An increased IgG response was observed following needle-free ID immunization of pigs. Nano-11 and cdAMP demonstrated a strong synergistic interaction, as shown in the activation of mouse, human, and porcine APC, with increased expression of costimulatory molecules and secretion of TNF and IL-1β. The combination adjuvant induced robust activation of both NF-κB and IFN regulatory factor signaling pathways and the NLRP3 inflammasome. We conclude that the combination of Nano-11 and cdAMP is a promising adjuvant for ID delivery of vaccines that supports a balanced immune response. |
| Databáze: | OpenAIRE |
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