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3M‐052 as an adjuvant for a PLGA microparticle‐based Leishmania donovani recombinant protein vaccine

2017; Wiley; Volume: 106; Issue: 4 Linguagem: Inglês

10.1002/jbm.b.33965

1552-4981

Qian Wang, Meagan A. Barry, Christopher A. Seid, Elissa M. Hudspeth, C. Patrick McAtee, Michael J. Heffernan,

Hepatitis Viruses Studies and Epidemiology

Abstract It is believed that an effective vaccine against leishmaniasis will require a T helper type 1 (T H 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 T H 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 T H 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.