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Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice
One of the proposed strategies for the development of a more efficient HIV-1 vaccine is based on the identification of proteins binding to a paratope of chosen broadly neutralizing antibody (bNAb) that will mimic cognate HIV-1 Env (glyco)protein epitope and could be used as potent immunogens for ind...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128222/ https://www.ncbi.nlm.nih.gov/pubmed/33993840 http://dx.doi.org/10.1080/21505594.2021.1920251 |
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author | Kuchař, Milan Kosztyu, Petr Daniel Lišková, Veronika Černý, Jiří Petroková, Hana Vróblová, Eliška Malý, Michal Vaňková, Lucie Křupka, Michal Rašková Kafková, Leona Turánek Knotigová, Pavlína Dušková, Jarmila Dohnálek, Jan Mašek, Josef Turánek, Jaroslav Raška, Milan Malý, Petr |
author_facet | Kuchař, Milan Kosztyu, Petr Daniel Lišková, Veronika Černý, Jiří Petroková, Hana Vróblová, Eliška Malý, Michal Vaňková, Lucie Křupka, Michal Rašková Kafková, Leona Turánek Knotigová, Pavlína Dušková, Jarmila Dohnálek, Jan Mašek, Josef Turánek, Jaroslav Raška, Milan Malý, Petr |
author_sort | Kuchař, Milan |
collection | PubMed |
description | One of the proposed strategies for the development of a more efficient HIV-1 vaccine is based on the identification of proteins binding to a paratope of chosen broadly neutralizing antibody (bNAb) that will mimic cognate HIV-1 Env (glyco)protein epitope and could be used as potent immunogens for induction of protective virus-neutralizing antibodies in the immunized individuals. To verify this “non-cognate ligand” concept, we developed a highly complex combinatorial library designed on a scaffold of human myomesin-1 protein domain and selected proteins called Myomedins specifically binding to variable regions of HIV-1 broadly neutralizing antibody 10E8. Immunization of mice with these Myomedin variants elicited the production of HIV-1 Env-specific antibodies. Hyperimmune sera bound to Env pseudotyped viruses and weakly/moderately neutralized 54% of tested clade A, B, C, and AE pseudotyped viruses variants in vitro. These results demonstrate that Myomedin variants have the potential to mimic Env epitopes and could be used as potential HIV-1 vaccine components. |
format | Online Article Text |
id | pubmed-8128222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-81282222021-05-21 Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice Kuchař, Milan Kosztyu, Petr Daniel Lišková, Veronika Černý, Jiří Petroková, Hana Vróblová, Eliška Malý, Michal Vaňková, Lucie Křupka, Michal Rašková Kafková, Leona Turánek Knotigová, Pavlína Dušková, Jarmila Dohnálek, Jan Mašek, Josef Turánek, Jaroslav Raška, Milan Malý, Petr Virulence Research Paper One of the proposed strategies for the development of a more efficient HIV-1 vaccine is based on the identification of proteins binding to a paratope of chosen broadly neutralizing antibody (bNAb) that will mimic cognate HIV-1 Env (glyco)protein epitope and could be used as potent immunogens for induction of protective virus-neutralizing antibodies in the immunized individuals. To verify this “non-cognate ligand” concept, we developed a highly complex combinatorial library designed on a scaffold of human myomesin-1 protein domain and selected proteins called Myomedins specifically binding to variable regions of HIV-1 broadly neutralizing antibody 10E8. Immunization of mice with these Myomedin variants elicited the production of HIV-1 Env-specific antibodies. Hyperimmune sera bound to Env pseudotyped viruses and weakly/moderately neutralized 54% of tested clade A, B, C, and AE pseudotyped viruses variants in vitro. These results demonstrate that Myomedin variants have the potential to mimic Env epitopes and could be used as potential HIV-1 vaccine components. Taylor & Francis 2021-05-16 /pmc/articles/PMC8128222/ /pubmed/33993840 http://dx.doi.org/10.1080/21505594.2021.1920251 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Kuchař, Milan Kosztyu, Petr Daniel Lišková, Veronika Černý, Jiří Petroková, Hana Vróblová, Eliška Malý, Michal Vaňková, Lucie Křupka, Michal Rašková Kafková, Leona Turánek Knotigová, Pavlína Dušková, Jarmila Dohnálek, Jan Mašek, Josef Turánek, Jaroslav Raška, Milan Malý, Petr Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice |
title | Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice |
title_full | Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice |
title_fullStr | Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice |
title_full_unstemmed | Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice |
title_short | Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice |
title_sort | myomedin scaffold variants targeted to 10e8 hiv-1 broadly neutralizing antibody mimic gp41 epitope and elicit hiv-1 virus-neutralizing sera in mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128222/ https://www.ncbi.nlm.nih.gov/pubmed/33993840 http://dx.doi.org/10.1080/21505594.2021.1920251 |
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