| Title | MIS416, a non-toxic microparticle adjuvant derived from Propionibacterium acnes comprising immunostimulatory muramyl dipeptide and bacterial DNA promotes cross-priming and Th1 immunity |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Girvan, R. C., Knight D. A., O'loughlin C. J., Hayman C. M., Hermans I. F., and Webster G. A. |
| IRL Team | Carbohydrate Chemistry |
| Journal | Vaccine |
| Volume | 29 |
| Pagination | 547-557 |
| Keywords | Adjuvants, animal, Animals, antibody conjugate, antigen presentation, antineoplastic activity, article, Bacterial, bacterial DNA, C57BL mouse, CD8+ T lymphocyte, CD8-Positive T-Lymphocytes, cell activation, cell maturation, cell selection, cell subpopulation, cell wall, cell wall skeleton, cellular immunity, chemistry, cross presentation, Cross-Priming, cytokine, cytokine release, Cytokines, cytotoxicity, dendritic cell, Dendritic Cells, DNA, DNA fragment, drug conjugation, drug delivery system, drug formulation, drug manufacture, drug safety, endocytosis, female, histopathology, human, Humans, Immunologic, immunological adjuvant, Immunology, immunostimulation, Inbred C57BL, isolation and purification, male, methodology, Mice, mis 416, mouse, muramyl dipeptide, myeloid dendritic cell, n acetylmuramylalanyl dextro isoglutamine, nonhuman, Ovalbumin, plasmacytoid dendritic cell, priority journal, Propionibacterium acnes, secretion, Th1 cell, Th1 Cells, unclassified drug, vaccination |
| Abstract | Propionibacterium acnes was modified using biochemical extraction methods generating a suspension of microparticles (MIS416) comprising a minimal cell wall skeleton rich in immunostimulatory crosslinked muramyl dipeptide repeats and native bacterial DNA fragments, each which have known adjuvant activity. In vitro studies demonstrated that MIS416 was readily internalized by human myeloid and plasmacytoid DC inducing cytokine secretion and cell activation/maturation. Vaccination studies in mice using OVA as a model antigen demonstrated that MIS416 acts as a Th1 adjuvant, promoting cross-priming of cytotoxic CD8+ T cell responses and enhanced anti-tumour immunity. Covalent attachment of OVA to MIS416 enabling simultaneous delivery of antigen and adjuvant to the antigen presentation system resulted in a dose-sparing vaccine formulation. Preclinical GLP toxicology studies demonstrated that MIS416 has a favorable safety profile in mouse and rabbit supporting its use in human vaccine formulations. © 2010 Elsevier Ltd. |
| URL | http://www.scopus.com/inward/record.url?eid=2-s2.0-78650520026&partnerID=40&md5=22b5200bb30e5c5eae11db9e2de60c96 |
| DOI | 10.1016/j.vaccine.2010.10.040 |
