Exploiting albumin as a mucosal vaccine chaperone for robust generation of lung-resident memory T cells
| Autor: | Nathan D. Donahue, Kelly D. Moynihan, Darrell J. Irvine, Wuhbet Abraham, Na Li, Alexis D. Baldeon, Chensu Wang, Kavya Rakhra |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CpG Oligodeoxynucleotide medicine.medical_treatment T cell Immunology Antigen presentation Priming (immunology) Lymphocyte Activation Article Immunophenotyping 03 medical and health sciences Memory T Cells Mice 0302 clinical medicine Antigen Adjuvants Immunologic T-Lymphocyte Subsets Albumins medicine Animals Immunity Mucosal Lung Mice Knockout Vaccines business.industry General Medicine Vaccination 030104 developmental biology medicine.anatomical_structure Immunization Organ Specificity 030220 oncology & carcinogenesis Host-Pathogen Interactions business Adjuvant Immunologic Memory Biomarkers |
| Zdroj: | Sci Immunol PMC |
| ISSN: | 2470-9468 |
| Popis: | Tissue-resident memory T cells (T(RMs)) can profoundly enhance mucosal immunity, but parameters governing T(RM) induction by vaccination remain poorly understood. Here we describe an approach exploiting natural albumin transport across the airway epithelium to enhance mucosal T(RM) generation by vaccination. Pulmonary immunization with albumin-binding amphiphile-conjugates of peptide antigens and CpG adjuvant (amph-vaccines) increased vaccine accumulation in the lung and mediastinal lymph nodes (MLNs). Amph-vaccines prolonged antigen presentation in MLNs over 2 weeks, leading to 25-fold increased lung-resident T-cell responses over traditional immunization and enhanced protection from viral or tumor challenge. Mimicking such prolonged exposure through repeated administration of soluble vaccine revealed that persistence of both antigen and adjuvant was critical for optimal T(RM) induction, mediated through T-cell priming in MLNs post prime, and directly in the lung tissue post boost. Thus, vaccine persistence strongly promotes T(RM) induction, and amph-conjugates may provide a practical approach to achieve such kinetics in mucosal vaccines. |
| Databáze: | OpenAIRE |
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