Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles

• Published in: International journal of molecular sciences 2023-03, Vol.24 (7), p.6183
• Main Authors: Veggi, Daniele, Dello Iacono, Lucia, Malito, Enrico, Maruggi, Giulietta, Giusti, Fabiola, Goswami, Panchali, Pansegrau, Werner, Marchi, Sara, Tomei, Sara, Luzzi, Enrico, Bottomley, Matthew James, Fontani, Federico, Ferlenghi, Ilaria, Scarselli, Maria
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antibodies; Antibodies, Blocking; Antigen presentation; Antigens; Antigens, Bacterial; Antigens, Viral; Arrays; Autoantigens; bacterial antigen; Bactericidal activity; Chromatography; Complement system; Electron microscopy; Ferritin; Ferritins; Glycoproteins; Immunogenicity; Influenza; Mice; Nanoparticles; Nanoparticles - chemistry; Neisseria meningitidis; Proteins; Self-assembly; Serum bactericidal activity; Severe acute respiratory syndrome coronavirus 2; Structural analysis; Technology application; Vaccines; Vaccines, Combined; Viral antibodies; Viral antigens; Virions
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076183

The presentation of viral antigens on nanoparticles in multivalent arrays has emerged as a valuable technology for vaccines. On the nanoparticle surface, highly ordered, repetitive arrays of antigens can mimic their geometric arrangement on virion surfaces and elicit stronger humoral responses than soluble viral antigens. More recently, bacterial antigens have been presented on self-assembling protein nanoparticles and have elicited protective antibody and effective T-helper responses, further supporting the nanoparticle platform as a universal approach for stimulating potent immunogenicity. Here, we present the rational design, structural analysis, and immunogenicity of self-assembling ferritin nanoparticles displaying eight copies of the trimeric adhesin NadA. We engineered constructs consisting of two different NadA fragments, head only and head with stalk, that we fused to ferritin and expressed in . Both fusion constructs self-assembled into the expected nanoparticles as determined by Cryo electron microscopy. In mice, the two nanoparticles elicited comparable NadA antibody levels that were 10- to 100-fold higher than those elicited by the corresponding NadA trimer subunits. Further, the NadAferritin nanoparticles potently induced complement-mediated serum bactericidal activity. These findings confirm the value of self-assembling nanoparticles for optimizing the immunogenicity of bacterial antigens and support the broad applicability of the approach to vaccine programs, especially for the presentation of trimeric antigens.