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- 2019
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas diseaseDOI: 10.1038/s41541-019-0107-7 Abstract: α1,3GalT-WT and α1,3GalT-KO mice exhibit different immune responses to T. cruzi infection. a Parasitemia in α1,3GalT-WT and α1,3GalT-KO mice infected (intraperitoneally (i.p.)) with 1?×?103 tissue culture-derived trypomastigotes (TCTs) (Y strain). b Kaplan–Meier survival rate curve of animals infected with 1?×?104 TCTs (Y strain). c Anti-α-Gal Ab levels as measured by chemiluminescent enzyme-linked immunosorbent assay using Galα3LN-BSA as antigen. RLU relative luminescence units. Infected C57BL/6 α1,3GalT-WT mice were compared to knockout (KO) mice by two-way analysis of variance (ANOVA) with Tukey’s multiple comparison test. *p?<?0.05; ****p?<?0.0001. d Serum cytokine profile of α1,3GalT-WT and α1,3GalT-KO mice infected (i.p.) with 1?×?103 TCTs and followed up for 28 days. N naive. Lysis of TCTs (1?×?107/mL) by serum e or purified anti-α-Gal Abs f from α1,3GalT-WT and α1,3GalT-KO mice infected (i.p.) with 1?×?103 TCTs. Unbound immunoglobulin G (IgG), non-anti-α-Gal IgG antibodies (Abs) (flow through) from Synsorb 115 immunoaffinity chromatography; anti-α-Gal IgG, anti-α-Gal Abs eluted from Synsorb 115. Inhibition of parasite host cell invasion g and intracellular amastigote proliferation h. LLC-MK2 cells were infected with Y strain TCTs (multiplicity of infection?=?10), for 2?h at 37?°C, in the presence or not of 100?μg/well of murine non-anti-α-Gal IgG Abs (Unbound IgG from Synsorb 115) or purified murine anti-α-Gal IgG Abs or control (None, medium alone). Number of infected cells per 1000 cells was evaluated after staining with 4,6-diamidino-2-phenylindole. a, b, f, g One-way ANOVA with Dunn’s multiple comparisons test. ***p?<?0.001; ****p?<?0.0001. The p values in a, b pertain to the mean values of the α1,3GalT-KO group in comparison with the α1,3GalT-WT throughout the course of the experiment. Error bars indicate S.E.
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