Dengue virus 2 lacking N153 glycosylation displayed enhanced recognition by neutralizing antibodies

Abstract Deglycosylated (N153Q) dengue virus (DENV) mutant shows attenuated infection in a mouse model, mainly due to its increased antibody susceptibility. This is consistent with the neutralization assay showing human monoclonal antibodies 2D22 and C10 are more potent towards the mutant than the wild-type (WT) virus. Here, we compared the cryoEM structures of WT and mutant viruses complexed with these Fabs at 37 °C (2.7–3.2 Å resolution). We observed increased occupancies for both Fabs on the mutant virus, suggesting higher accessibility of epitopes that were previously blocked by glycosylation. Using biolayer interferometry, we showed that at 30 °C, the antibodies exhibited a slower binding rate with the mutant than with WT virus, along with a slower dissociation rate. However, at 37 °C, the affinities of both antibodies for DENV2 WT and N153Q increased significantly. N153Q mutant might be a good vaccine candidate, as important epitopes are made more accessible for stimulating highly potent antibodies.