Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA

Structural knowledge of antigens in their native state can drive the design of optimized vaccine antigens that mimic the native epitope exposure and conformation. Here, by hydrogen-deuterium exchange mass spectrometry, we assessed the structural features of Neisseria Adhesin A (NadA), a meningococcal trimeric outer membrane protein, included as soluble recombinant antigen in the 4CMenB vaccine. We propose a structural annotation of the recombinant NadA and compare its structural dynamics with NadA in situ, as embedded in meningococcal outer membrane vesicles (OMVs). The observed conformational differences suggest that OMV-embedded NadA could be more susceptible to trimer opening and display a larger antigenic surface than the soluble antigen. Accordingly, mice immunized with OMV-embedded NadA elicited antibodies with superior bactericidal activity compared to the soluble antigen. Collectively, these data support the hypothesis that protein vaccine antigens presented in native-like environments can elicit a more potent immune response than recombinant forms.