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Myomedin replicas of gp120 V3 loop glycan epitopes recognized by PGT121 and PGT126 antibodies as non-cognate antigens for stimulation of HIV-1 broadly neutralizing antibodies.
Daniel Lisková, Veronika; Kosztyu, Petr; Kuchar, Milan; Cerný, Jirí; Bharadwaj, Shiv; Petroková, Hana; Vroblová, Eliska; Krupka, Michal; Malý, Michal; Zosincuková, Tereza; Sulc, Josef; Rasková Kafková, Leona; Raska, Milan; Malý, Petr.
Afiliación
  • Daniel Lisková V; Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Kosztyu P; Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia.
  • Kuchar M; Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Cerný J; Laboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Bharadwaj S; Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Petroková H; Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Vroblová E; Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia.
  • Krupka M; Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia.
  • Malý M; Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Zosincuková T; Laboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Sulc J; Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Rasková Kafková L; Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia.
  • Raska M; Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia.
  • Malý P; Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia.
Front Immunol ; 13: 1066361, 2022.
Article en En | MEDLINE | ID: mdl-36569830
Introduction: Imprinting broadly neutralizing antibody (bNAb) paratopes by shape complementary protein mimotopes represents a potential alternative for developing vaccine immunogens. This approach, designated as a Non-Cognate Ligand Strategy (NCLS), has recently been used for the identification of protein variants mimicking CD4 binding region epitope or membrane proximal external region (MPER) epitope of HIV-1 envelope (Env) glycoprotein. However, the potential of small binding proteins to mimic viral glycan-containing epitopes has not yet been verified. Methods: In this work, we employed a highly complex combinatorial Myomedin scaffold library to identify variants recognizing paratopes of super candidate bNAbs, PGT121 and PGT126, specific for HIV-1 V3 loop epitopes. Results: In the collection of Myomedins called MLD variants targeted to PGT121, three candidates competed with gp120 for binding to this bNAb in ELISA, thus suggesting an overlapping binding site and epitope-mimicking potential. Myomedins targeted to PGT126 designated MLB also provided variants that competed with gp120. Immunization of mice with MLB or MLD binders resulted in the production of anti-gp120 and -Env serum antibodies. Mouse hyper-immune sera elicited with MLB036, MLB041, MLB049, and MLD108 moderately neutralized 8-to-10 of 22 tested HIV-1-pseudotyped viruses of A, B, and C clades in vitro. Discussion: Our data demonstrate that Myomedin-derived variants can mimic particular V3 glycan epitopes of prominent anti-HIV-1 bNAbs, ascertain the potential of particular glycans controlling neutralizing sensitivity of individual HIV-1 pseudoviruses, and represent promising prophylactic candidates for HIV-1 vaccine development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / VIH-1 Límite: Animals Idioma: En Revista: Front Immunol Año: 2022 Tipo del documento: Article Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / VIH-1 Límite: Animals Idioma: En Revista: Front Immunol Año: 2022 Tipo del documento: Article Pais de publicación: Suiza