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

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.