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Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti

The significant rise in the number of tick-borne diseases represents a major threat to public health worldwide. One such emerging disease is human babesiosis, which is caused by several protozoan parasites of the Babesia genus of which B. microti is responsible for most clinical cases reported to da...

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Autores principales: Chand, Meenal, Choi, Jae-Yeon, Pal, Anasuya C., Singh, Pallavi, Kumari, Vandana, Thekkiniath, Jose, Gagnon, Jacqueline, Timalsina, Sushma, Gaur, Gauri, Williams, Scott, Ledizet, Michel, Mamoun, Choukri Ben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732259/
https://www.ncbi.nlm.nih.gov/pubmed/36506011
http://dx.doi.org/10.3389/fcimb.2022.1039197
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author Chand, Meenal
Choi, Jae-Yeon
Pal, Anasuya C.
Singh, Pallavi
Kumari, Vandana
Thekkiniath, Jose
Gagnon, Jacqueline
Timalsina, Sushma
Gaur, Gauri
Williams, Scott
Ledizet, Michel
Mamoun, Choukri Ben
author_facet Chand, Meenal
Choi, Jae-Yeon
Pal, Anasuya C.
Singh, Pallavi
Kumari, Vandana
Thekkiniath, Jose
Gagnon, Jacqueline
Timalsina, Sushma
Gaur, Gauri
Williams, Scott
Ledizet, Michel
Mamoun, Choukri Ben
author_sort Chand, Meenal
collection PubMed
description The significant rise in the number of tick-borne diseases represents a major threat to public health worldwide. One such emerging disease is human babesiosis, which is caused by several protozoan parasites of the Babesia genus of which B. microti is responsible for most clinical cases reported to date. Recent studies have shown that during its intraerythrocytic life cycle, B. microti exports several antigens into the mammalian host using a novel vesicular-mediated secretion mechanism. One of these secreted proteins is the immunodominant antigen BmGPI12, which has been demonstrated to be a reliable biomarker of active B. microti infection. The major immunogenic determinants of this antigen remain unknown. Here we provide a comprehensive molecular and serological characterization of a set of eighteen monoclonal antibodies developed against BmGPI12 and a detailed profile of their binding specificity and suitability in the detection of active B. microti infection. Serological profiling and competition assays using synthetic peptides identified five unique epitopes on the surface of BmGPI12 which are recognized by a set of eight monoclonal antibodies. ELISA-based antigen detection assays identified five antibody combinations that specifically detect the secreted form of BmGPI12 in plasma samples from B. microti-infected mice and humans but not from other Babesia species or P. falciparum.
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spelling pubmed-97322592022-12-10 Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti Chand, Meenal Choi, Jae-Yeon Pal, Anasuya C. Singh, Pallavi Kumari, Vandana Thekkiniath, Jose Gagnon, Jacqueline Timalsina, Sushma Gaur, Gauri Williams, Scott Ledizet, Michel Mamoun, Choukri Ben Front Cell Infect Microbiol Cellular and Infection Microbiology The significant rise in the number of tick-borne diseases represents a major threat to public health worldwide. One such emerging disease is human babesiosis, which is caused by several protozoan parasites of the Babesia genus of which B. microti is responsible for most clinical cases reported to date. Recent studies have shown that during its intraerythrocytic life cycle, B. microti exports several antigens into the mammalian host using a novel vesicular-mediated secretion mechanism. One of these secreted proteins is the immunodominant antigen BmGPI12, which has been demonstrated to be a reliable biomarker of active B. microti infection. The major immunogenic determinants of this antigen remain unknown. Here we provide a comprehensive molecular and serological characterization of a set of eighteen monoclonal antibodies developed against BmGPI12 and a detailed profile of their binding specificity and suitability in the detection of active B. microti infection. Serological profiling and competition assays using synthetic peptides identified five unique epitopes on the surface of BmGPI12 which are recognized by a set of eight monoclonal antibodies. ELISA-based antigen detection assays identified five antibody combinations that specifically detect the secreted form of BmGPI12 in plasma samples from B. microti-infected mice and humans but not from other Babesia species or P. falciparum. Frontiers Media S.A. 2022-11-25 /pmc/articles/PMC9732259/ /pubmed/36506011 http://dx.doi.org/10.3389/fcimb.2022.1039197 Text en Copyright © 2022 Chand, Choi, Pal, Singh, Kumari, Thekkiniath, Gagnon, Timalsina, Gaur, Williams, Ledizet and Mamoun https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Chand, Meenal
Choi, Jae-Yeon
Pal, Anasuya C.
Singh, Pallavi
Kumari, Vandana
Thekkiniath, Jose
Gagnon, Jacqueline
Timalsina, Sushma
Gaur, Gauri
Williams, Scott
Ledizet, Michel
Mamoun, Choukri Ben
Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
title Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
title_full Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
title_fullStr Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
title_full_unstemmed Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
title_short Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
title_sort epitope profiling of monoclonal antibodies to the immunodominant antigen bmgpi12 of the human pathogen babesia microti
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732259/
https://www.ncbi.nlm.nih.gov/pubmed/36506011
http://dx.doi.org/10.3389/fcimb.2022.1039197
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