Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies

The development of antibodies against specific glycan epitopes poses a significant challenge due to difficulties obtaining desired glycans at sufficient quantity and purity, and the fact that glycans are usually weakly immunogenic. To address this challenge, we leveraged the potent immunostimulatory activity of bacterial outer membrane vesicles (OMVs) to deliver designer glycan epitopes to the immune system. This approach involved heterologous expression of two clinically important glycans, namely polysialic acid (PSA) and Thomsen-Friedenreich antigen (T antigen) in hypervesiculating strains of non-pathogenic Escherichia coli. The resulting glycOMVs displayed structural mimics of PSA or T antigen on their surfaces, and induced high titers of glycan-specific IgG antibodies following immunization in mice. In the case of PSA glycOMVs, serum antibodies potently killed Neisseria meningitidis serogroup B (MenB), whose outer capsule is PSA, in a serum bactericidal assay. These findings demonstrate the potential of glycOMVs for inducing class-switched, humoral immune responses against glycan antigens. [Display omitted] •OMV formation can be coupled with designer glycan biosynthesis in E. coli bacteria•Glycosylated OMVs (glycOMVs) display structural mimics of foreign glycan structures•GlycOMVs stimulate high titers of class-switched, glycan-specific IgG antibodies•GlycOMVs as a modular platform for targeting numerous biomedically relevant glycans Valentine et al. demonstrate that outer membrane vesicles displaying heterologous glycans on their exterior are potent stimulators of class-switched, glycan-specific humoral immune responses, signaling the possibility of glycosylated OMVs (glycOMVs) as a robust and tunable platform for generating antibodies against numerous biomedically relevant glycan epitopes.