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Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens

Burkholderia pseudomallei is an infectious bacterium of clinical and biodefense concern, and is the causative agent of melioidosis. The mortality rate can reach up to 50% and affects 165,000 people per year; however, there is currently no vaccine available. In this study, we examine the antigen-spec...

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Autores principales: Grund, Megan E., Kramarska, Eliza, Choi, Soo Jeon, McNitt, Dudley H., Klimko, Christopher P., Rill, Nathaniel O., Dankmeyer, Jennifer L., Shoe, Jennifer L., Hunter, Melissa, Fetterer, David P., Hedrick, Zander M., Velez, Ivan, Biryukov, Sergei S., Cote, Christopher K., Berisio, Rita, Lukomski, Slawomir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621890/
https://www.ncbi.nlm.nih.gov/pubmed/34835150
http://dx.doi.org/10.3390/vaccines9111219
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author Grund, Megan E.
Kramarska, Eliza
Choi, Soo Jeon
McNitt, Dudley H.
Klimko, Christopher P.
Rill, Nathaniel O.
Dankmeyer, Jennifer L.
Shoe, Jennifer L.
Hunter, Melissa
Fetterer, David P.
Hedrick, Zander M.
Velez, Ivan
Biryukov, Sergei S.
Cote, Christopher K.
Berisio, Rita
Lukomski, Slawomir
author_facet Grund, Megan E.
Kramarska, Eliza
Choi, Soo Jeon
McNitt, Dudley H.
Klimko, Christopher P.
Rill, Nathaniel O.
Dankmeyer, Jennifer L.
Shoe, Jennifer L.
Hunter, Melissa
Fetterer, David P.
Hedrick, Zander M.
Velez, Ivan
Biryukov, Sergei S.
Cote, Christopher K.
Berisio, Rita
Lukomski, Slawomir
author_sort Grund, Megan E.
collection PubMed
description Burkholderia pseudomallei is an infectious bacterium of clinical and biodefense concern, and is the causative agent of melioidosis. The mortality rate can reach up to 50% and affects 165,000 people per year; however, there is currently no vaccine available. In this study, we examine the antigen-specific immune response to a vaccine formulated with antigens derived from an outer membrane protein in B. pseudomallei, Bucl8. Here, we employed a number of bioinformatic tools to predict Bucl8-derived epitopes that are non-allergenic and non-toxic, but would elicit an immune response. From these data, we formulated a vaccine based on two extracellular components of Bucl8, the β-barrel loops and extended collagen and non-collagen domains. Outbred CD-1 mice were immunized with vaccine formulations—composed of recombinant proteins or conjugated synthetic peptides with adjuvant—to assess the antigen-specific immune responses in mouse sera and lymphoid organs. We found that mice vaccinated with either Bucl8-derived components generated a robust TH2-skewed antibody response when antigen was combined with the adjuvant AddaVax, while the TH1 response was limited. Mice immunized with synthetic loop peptides had a stronger, more consistent antibody response than recombinant protein antigens, based on higher IgG titers and recognition of bacteria. We then compared peptide-based vaccines in an established C57BL/6 inbred mouse model and observed a similar TH2-skewed response. The resulting formulations will be applied in future studies examining the protection of Bucl8-derived vaccines.
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spelling pubmed-86218902021-11-27 Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens Grund, Megan E. Kramarska, Eliza Choi, Soo Jeon McNitt, Dudley H. Klimko, Christopher P. Rill, Nathaniel O. Dankmeyer, Jennifer L. Shoe, Jennifer L. Hunter, Melissa Fetterer, David P. Hedrick, Zander M. Velez, Ivan Biryukov, Sergei S. Cote, Christopher K. Berisio, Rita Lukomski, Slawomir Vaccines (Basel) Communication Burkholderia pseudomallei is an infectious bacterium of clinical and biodefense concern, and is the causative agent of melioidosis. The mortality rate can reach up to 50% and affects 165,000 people per year; however, there is currently no vaccine available. In this study, we examine the antigen-specific immune response to a vaccine formulated with antigens derived from an outer membrane protein in B. pseudomallei, Bucl8. Here, we employed a number of bioinformatic tools to predict Bucl8-derived epitopes that are non-allergenic and non-toxic, but would elicit an immune response. From these data, we formulated a vaccine based on two extracellular components of Bucl8, the β-barrel loops and extended collagen and non-collagen domains. Outbred CD-1 mice were immunized with vaccine formulations—composed of recombinant proteins or conjugated synthetic peptides with adjuvant—to assess the antigen-specific immune responses in mouse sera and lymphoid organs. We found that mice vaccinated with either Bucl8-derived components generated a robust TH2-skewed antibody response when antigen was combined with the adjuvant AddaVax, while the TH1 response was limited. Mice immunized with synthetic loop peptides had a stronger, more consistent antibody response than recombinant protein antigens, based on higher IgG titers and recognition of bacteria. We then compared peptide-based vaccines in an established C57BL/6 inbred mouse model and observed a similar TH2-skewed response. The resulting formulations will be applied in future studies examining the protection of Bucl8-derived vaccines. MDPI 2021-10-20 /pmc/articles/PMC8621890/ /pubmed/34835150 http://dx.doi.org/10.3390/vaccines9111219 Text en © 2021 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 Communication
Grund, Megan E.
Kramarska, Eliza
Choi, Soo Jeon
McNitt, Dudley H.
Klimko, Christopher P.
Rill, Nathaniel O.
Dankmeyer, Jennifer L.
Shoe, Jennifer L.
Hunter, Melissa
Fetterer, David P.
Hedrick, Zander M.
Velez, Ivan
Biryukov, Sergei S.
Cote, Christopher K.
Berisio, Rita
Lukomski, Slawomir
Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens
title Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens
title_full Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens
title_fullStr Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens
title_full_unstemmed Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens
title_short Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens
title_sort predictive and experimental immunogenicity of burkholderia collagen-like protein 8-derived antigens
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621890/
https://www.ncbi.nlm.nih.gov/pubmed/34835150
http://dx.doi.org/10.3390/vaccines9111219
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