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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

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    SYSNO ASEP0549194
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleMyomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice
    Author(s) Kuchař, Milan (BTO-N) RID
    Kosztyu, P. (CZ)
    Daniel Lišková, Veronika (BTO-N)
    Černý, Jiří (BTO-N) RID, ORCID
    Petroková, Hana (BTO-N) RID
    Vroblova, E. (CZ)
    Malý, Michal (BTO-N)
    Vaňková, Lucie (BTO-N)
    Krupka, M. (CZ)
    Raskova Kafkova, L. (CZ)
    Turánek Knotigová, P. (CZ)
    Dušková, Jarmila (BTO-N) RID, SAI
    Dohnálek, Jan (BTO-N) RID, ORCID
    Mašek, J. (CZ)
    Turánek, J. (CZ)
    Raška, M. (CZ)
    Malý, Petr (BTO-N) RID, ORCID
    Number of authors17
    Source TitleVirulence. - : Taylor & Francis - ISSN 2150-5594
    Roč. 12, č. 1 (2021), s. 1271-1287
    Number of pages17 s.
    Languageeng - English
    CountryUS - United States
    Keywordsprotein scaffold ; combinatorial library ; protein mimetics ; Env glycoprotein
    Subject RIVFN - Epidemiology, Contagious Diseases ; Clinical Immunology
    OECD categoryInfectious Diseases
    R&D ProjectsNV15-32198A GA MZd - Ministry of Health (MZ)
    EF16_025/0007397 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Method of publishingOpen access
    Institutional supportBTO-N - RVO:86652036
    UT WOS000650967900001
    EID SCOPUS85105945438
    DOI10.1080/21505594.2021.1920251
    AnnotationOne 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.
    WorkplaceInstitute of Biotechnology
    ContactMonika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
    Year of Publishing2022
    Electronic addresshttps://www.tandfonline.com/doi/full/10.1080/21505594.2021.1920251
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