3M-052 as an adjuvant for a PLGA microparticle-based Leishmania donovani recombinant protein vaccine
| Autor: | Christopher A. Seid, Elissa M. Hudspeth, Qian Wang, Meagan A. Barry, C. Patrick McAtee, Michael J. Heffernan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Molybdoferredoxin Materials science medicine.medical_treatment Dose-Response Relationship Immunologic Protozoan Proteins Biomedical Engineering Leishmania donovani Antigens Protozoan Pharmacology Microbiology Biomaterials Mice 03 medical and health sciences chemistry.chemical_compound Immunogenicity Vaccine Immune system Polylactic Acid-Polyglycolic Acid Copolymer Antigen medicine Animals Leishmaniasis Vaccines Mice Inbred BALB C biology Immunogenicity biology.organism_classification Recombinant Proteins PLGA 030104 developmental biology chemistry biology.protein Leishmaniasis Visceral Antibody Heterocyclic Compounds 3-Ring Adjuvant Stearic Acids |
| Zdroj: | Journal of Biomedical Materials Research Part B: Applied Biomaterials. 106:1587-1594 |
| ISSN: | 1552-4973 |
| Popis: | It is believed that an effective vaccine against leishmaniasis will require a T helper type 1 (TH 1) immune response. In this study, we investigated the adjuvanticity of the Toll-like receptor (TLR) 7/8 agonist 3M-052 in combination with the Leishmania donovani 36-kDa nucleoside hydrolase recombinant protein antigen (NH36). NH36 and 3M-052 were encapsulated in separate batches of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). The loading efficiency for NH36 was 83% and for 3M-052 was above 95%. In vitro stimulation of bone marrow-derived dendritic cells, measured by IL-12 secretion, demonstrated that 3M-052 (free or MP-formulated) had a concentration-dependent immunostimulatory effect with an optimum concentration of 2 µg/mL. In immunogenicity studies in BALB/c mice, MP-formulated NH36 and 3M-052 elicited the highest serum titers of TH 1-associated IgG2a and IgG2b antibodies and the highest frequency of IFNγ-producing splenocytes. No dose dependency was observed among MP/NH36/3M-052 groups over a dose range of 4-60 µg 3M-052 per injection. The ability of MP-formulated NH36 and 3M-052 to elicit a TH 1-biased immune response indicates the potential for PLGA MP-formulated 3M-052 to be used as an adjuvant for leishmaniasis vaccines. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1587-1594, 2018. |
| Databáze: | OpenAIRE |
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