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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093968/
https://www.ncbi.nlm.nih.gov/pubmed/37047152
http://dx.doi.org/10.3390/ijms24076183
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author 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
author_facet 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
author_sort Veggi, Daniele
collection PubMed
description 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 Neisseria meningitidis 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 Escherichia coli. 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.
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spelling pubmed-100939682023-04-13 Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles 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 Int J Mol Sci Article 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 Neisseria meningitidis 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 Escherichia coli. 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. MDPI 2023-03-24 /pmc/articles/PMC10093968/ /pubmed/37047152 http://dx.doi.org/10.3390/ijms24076183 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles
title Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles
title_full Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles
title_fullStr Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles
title_full_unstemmed Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles
title_short Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles
title_sort effective multivalent oriented presentation of meningococcal nada antigen trimers by self-assembling ferritin nanoparticles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093968/
https://www.ncbi.nlm.nih.gov/pubmed/37047152
http://dx.doi.org/10.3390/ijms24076183
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