Predictive and Experimental Immunogenicity of <i>Burkholderia</i> Collagen-like Protein 8-Derived Antigens

<i>Burkholderia pseudomallei</i> 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 exami...

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Autores principales: Megan E. Grund, Eliza Kramarska, Soo Jeon Choi, Dudley H. McNitt, Christopher P. Klimko, Nathaniel O. Rill, Jennifer L. Dankmeyer, Jennifer L. Shoe, Melissa Hunter, David P. Fetterer, Zander M. Hedrick, Ivan Velez, Sergei S. Biryukov, Christopher K. Cote, Rita Berisio, Slawomir Lukomski
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/f0325049872148c6b26d2abf44affa70
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spelling oai:doaj.org-article:f0325049872148c6b26d2abf44affa702021-11-25T19:10:09ZPredictive and Experimental Immunogenicity of <i>Burkholderia</i> Collagen-like Protein 8-Derived Antigens10.3390/vaccines91112192076-393Xhttps://doaj.org/article/f0325049872148c6b26d2abf44affa702021-10-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1219https://doaj.org/toc/2076-393X<i>Burkholderia pseudomallei</i> 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 <i>B. pseudomallei</i>, 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.Megan E. GrundEliza KramarskaSoo Jeon ChoiDudley H. McNittChristopher P. KlimkoNathaniel O. RillJennifer L. DankmeyerJennifer L. ShoeMelissa HunterDavid P. FettererZander M. HedrickIvan VelezSergei S. BiryukovChristopher K. CoteRita BerisioSlawomir LukomskiMDPI AGarticlevaccineBucl8subunit vaccineantigenicityimmunogenicityMedicineRENVaccines, Vol 9, Iss 1219, p 1219 (2021)
institution DOAJ
collection DOAJ
language EN
topic vaccine
Bucl8
subunit vaccine
antigenicity
immunogenicity
Medicine
R
spellingShingle vaccine
Bucl8
subunit vaccine
antigenicity
immunogenicity
Medicine
R
Megan E. Grund
Eliza Kramarska
Soo Jeon Choi
Dudley H. McNitt
Christopher P. Klimko
Nathaniel O. Rill
Jennifer L. Dankmeyer
Jennifer L. Shoe
Melissa Hunter
David P. Fetterer
Zander M. Hedrick
Ivan Velez
Sergei S. Biryukov
Christopher K. Cote
Rita Berisio
Slawomir Lukomski
Predictive and Experimental Immunogenicity of <i>Burkholderia</i> Collagen-like Protein 8-Derived Antigens
description <i>Burkholderia pseudomallei</i> 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 <i>B. pseudomallei</i>, 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.
format article
author Megan E. Grund
Eliza Kramarska
Soo Jeon Choi
Dudley H. McNitt
Christopher P. Klimko
Nathaniel O. Rill
Jennifer L. Dankmeyer
Jennifer L. Shoe
Melissa Hunter
David P. Fetterer
Zander M. Hedrick
Ivan Velez
Sergei S. Biryukov
Christopher K. Cote
Rita Berisio
Slawomir Lukomski
author_facet Megan E. Grund
Eliza Kramarska
Soo Jeon Choi
Dudley H. McNitt
Christopher P. Klimko
Nathaniel O. Rill
Jennifer L. Dankmeyer
Jennifer L. Shoe
Melissa Hunter
David P. Fetterer
Zander M. Hedrick
Ivan Velez
Sergei S. Biryukov
Christopher K. Cote
Rita Berisio
Slawomir Lukomski
author_sort Megan E. Grund
title Predictive and Experimental Immunogenicity of <i>Burkholderia</i> Collagen-like Protein 8-Derived Antigens
title_short Predictive and Experimental Immunogenicity of <i>Burkholderia</i> Collagen-like Protein 8-Derived Antigens
title_full Predictive and Experimental Immunogenicity of <i>Burkholderia</i> Collagen-like Protein 8-Derived Antigens
title_fullStr Predictive and Experimental Immunogenicity of <i>Burkholderia</i> Collagen-like Protein 8-Derived Antigens
title_full_unstemmed Predictive and Experimental Immunogenicity of <i>Burkholderia</i> Collagen-like Protein 8-Derived Antigens
title_sort predictive and experimental immunogenicity of <i>burkholderia</i> collagen-like protein 8-derived antigens
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/f0325049872148c6b26d2abf44affa70
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