Cell recruitment and antigen trafficking in afferent lymph after injection of antigen and poly(I:C) containing liposomes, in aqueous or oil-based formulations
| Autor: | Jackie Nathanielsz, Martin J Elhay, Melanie R Neeland, Jill Louise Pleasance, Michael John de Veer, Elza Nicole Theresia Meeusen, Melissa Louise Burke |
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| Rok vydání: | 2013 |
| Předmět: |
Time Factors
Diphtheria Toxoid Injections Subcutaneous medicine.medical_treatment Cell Immune system Adjuvants Immunologic Antigen Leukocytes medicine Animals Lymph node Liposome General Veterinary General Immunology and Microbiology business.industry Public Health Environmental and Occupational Health Dendritic Cells Cell biology Poly I-C Infectious Diseases medicine.anatomical_structure Lymphatic system Liposomes Immunology Molecular Medicine Emulsions Lymph business Oils Adjuvant |
| Zdroj: | Vaccine. 31:1012-1018 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2012.12.049 |
| Popis: | a b s t r a c t After vaccination, innate cell populations transport antigen from the tissue, via the afferent lymphatic vessels, into the local lymph node where they provide critical signals for the generation of an adap- tive immune response. The present study uses a unique lymphatic cannulation model to examine, in real time, changes in afferent lymph after injection of a liposome-based delivery system, incorporating diptheria toxoid (DT) and the innate stimulator, poly(I:C). There was a dramatic but temporal recruitment of innate cell populations over time, with neutrophils and monocytes peaking at 6 h and 28 h post vacci- nation respectively. The number of dendritic cells (DC) did not increase over the 198 h time period, while lymphocytes were slightly elevated at the latest times, indicating the start of an adaptive response. Mono- cytes and neutrophils were the predominant cell types transporting antigen at the early time points while DC were the most dominant antigen-carrying cells after 78 h, predominantly the Sirp- high DC subtype. Resuspending liposomes in oil instead of aqueous solutions has recently been shown to dramatically increase the level and persistence of an immune response and forms the basis of the novel adjuvant formulations, Vaccimax© and Depovax©. In the present study, formulation of the DT and poly(I:C) con- taining liposomes in an oil carrier dramatically reduced antigen transport to the draining lymph nodes. Examination of the injection site revealed the creation of an ectopic lymphoid tissue with prominent antigen foci and organized lymphoid cells, providing a possible mechanism for the persistence of an immune response in liposome-in-oil adjuvant formulation. Together, the present studies demonstrate the real-time innate in vivo response to vaccination of two novel liposome-based adjuvant systems and the dramatic effect of different carrier formulations. |
| Databáze: | OpenAIRE |
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