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Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity

Self-assembling protein nanoparticles (SAPN) serve as a repetitive antigen delivery platform with high-density epitope display; however, antigen characteristics such as size and epitope presentation can influence the immunogenicity of the assembled particle and are aspects to consider for a rational...

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Autores principales: Schneider, Cosette G., Taylor, Justin A., Sibilo, Michael Q., Miura, Kazutoyo, Mallory, Katherine L., Mann, Christopher, Karch, Christopher, Beck, Zoltan, Matyas, Gary R., Long, Carole A., Bergmann-Leitner, Elke, Burkhard, Peter, Angov, Evelina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911071/
https://www.ncbi.nlm.nih.gov/pubmed/33572803
http://dx.doi.org/10.3390/vaccines9020103
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author Schneider, Cosette G.
Taylor, Justin A.
Sibilo, Michael Q.
Miura, Kazutoyo
Mallory, Katherine L.
Mann, Christopher
Karch, Christopher
Beck, Zoltan
Matyas, Gary R.
Long, Carole A.
Bergmann-Leitner, Elke
Burkhard, Peter
Angov, Evelina
author_facet Schneider, Cosette G.
Taylor, Justin A.
Sibilo, Michael Q.
Miura, Kazutoyo
Mallory, Katherine L.
Mann, Christopher
Karch, Christopher
Beck, Zoltan
Matyas, Gary R.
Long, Carole A.
Bergmann-Leitner, Elke
Burkhard, Peter
Angov, Evelina
author_sort Schneider, Cosette G.
collection PubMed
description Self-assembling protein nanoparticles (SAPN) serve as a repetitive antigen delivery platform with high-density epitope display; however, antigen characteristics such as size and epitope presentation can influence the immunogenicity of the assembled particle and are aspects to consider for a rationally designed effective vaccine. Here, we characterize the folding and immunogenicity of heterogeneous antigen display by integrating (a) dual-stage antigen SAPN presenting the P. falciparum (Pf) merozoite surface protein 1 subunit, PfMSP1(19), and Pf cell-traversal protein for ookinetes and sporozoites, PfCelTOS, in addition to (b) a homogenous antigen SAPN displaying two copies of PfCelTOS. Mice and rabbits were utilized to evaluate antigen-specific humoral and cellular induction as well as functional antibodies via growth inhibition of the blood-stage parasite. We demonstrate that antigen orientation and folding influence the elicited immune response, and when appropriately designed, SAPN can serve as an adaptable platform for an effective multi-antigen display.
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spelling pubmed-79110712021-02-28 Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity Schneider, Cosette G. Taylor, Justin A. Sibilo, Michael Q. Miura, Kazutoyo Mallory, Katherine L. Mann, Christopher Karch, Christopher Beck, Zoltan Matyas, Gary R. Long, Carole A. Bergmann-Leitner, Elke Burkhard, Peter Angov, Evelina Vaccines (Basel) Article Self-assembling protein nanoparticles (SAPN) serve as a repetitive antigen delivery platform with high-density epitope display; however, antigen characteristics such as size and epitope presentation can influence the immunogenicity of the assembled particle and are aspects to consider for a rationally designed effective vaccine. Here, we characterize the folding and immunogenicity of heterogeneous antigen display by integrating (a) dual-stage antigen SAPN presenting the P. falciparum (Pf) merozoite surface protein 1 subunit, PfMSP1(19), and Pf cell-traversal protein for ookinetes and sporozoites, PfCelTOS, in addition to (b) a homogenous antigen SAPN displaying two copies of PfCelTOS. Mice and rabbits were utilized to evaluate antigen-specific humoral and cellular induction as well as functional antibodies via growth inhibition of the blood-stage parasite. We demonstrate that antigen orientation and folding influence the elicited immune response, and when appropriately designed, SAPN can serve as an adaptable platform for an effective multi-antigen display. MDPI 2021-01-29 /pmc/articles/PMC7911071/ /pubmed/33572803 http://dx.doi.org/10.3390/vaccines9020103 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schneider, Cosette G.
Taylor, Justin A.
Sibilo, Michael Q.
Miura, Kazutoyo
Mallory, Katherine L.
Mann, Christopher
Karch, Christopher
Beck, Zoltan
Matyas, Gary R.
Long, Carole A.
Bergmann-Leitner, Elke
Burkhard, Peter
Angov, Evelina
Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity
title Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity
title_full Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity
title_fullStr Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity
title_full_unstemmed Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity
title_short Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity
title_sort orientation of antigen display on self-assembling protein nanoparticles influences immunogenicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911071/
https://www.ncbi.nlm.nih.gov/pubmed/33572803
http://dx.doi.org/10.3390/vaccines9020103
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