Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

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

V. Daniel Lišková, P. Kosztyu, M. Kuchař, J. Černý, S. Bharadwaj, H. Petroková, E. Vroblová, M. Křupka, M. Malý, T. Zosinčuková, J. Šulc, L. Rašková Kafková, M. Raška, P. Malý

. 2022 ; 13 (-) : 1066361. [pub] 20221208

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22032219

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22032219
003      
CZ-PrNML
005      
20230131151355.0
007      
ta
008      
230120s2022 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3389/fimmu.2022.1066361 $2 doi
035    __
$a (PubMed)36569830
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Daniel Lišková, Veronika $u Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
245    10
$a 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 / $c V. Daniel Lišková, P. Kosztyu, M. Kuchař, J. Černý, S. Bharadwaj, H. Petroková, E. Vroblová, M. Křupka, M. Malý, T. Zosinčuková, J. Šulc, L. Rašková Kafková, M. Raška, P. Malý
520    9_
$a 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.
650    _2
$a zvířata $7 D000818
650    _2
$a myši $7 D051379
650    _2
$a epitopy $7 D000939
650    _2
$a široce neutralizující protilátky $7 D000080908
650    12
$a HIV protilátky $7 D015483
650    _2
$a neutralizující protilátky $7 D057134
650    _2
$a HIV obalový protein gp120 $7 D015699
650    12
$a HIV-1 $7 D015497
650    _2
$a polysacharidy $7 D011134
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Kosztyu, Petr $u Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia
700    1_
$a Kuchař, Milan $u Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
700    1_
$a Černý, Jiří $u Laboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
700    1_
$a Bharadwaj, Shiv $u Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
700    1_
$a Petroková, Hana $u Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
700    1_
$a Vroblová, Eliška $u Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia
700    1_
$a Křupka, Michal $u Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia
700    1_
$a Malý, Michal $u Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia $u Laboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
700    1_
$a Zosinčuková, Tereza $u Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
700    1_
$a Šulc, Josef $u Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
700    1_
$a Rašková Kafková, Leona $u Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia
700    1_
$a Raška, Milan $u Department of Immunology, Palacky University Olomouc, Hnevotinska, Olomouc, Czechia
700    1_
$a Malý, Petr $u Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova, Vestec, Czechia
773    0_
$w MED00181405 $t Frontiers in immunology $x 1664-3224 $g Roč. 13, č. - (2022), s. 1066361
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36569830 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230120 $b ABA008
991    __
$a 20230131151351 $b ABA008
999    __
$a ok $b bmc $g 1891150 $s 1183554
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2022 $b 13 $c - $d 1066361 $e 20221208 $i 1664-3224 $m Frontiers in immunology $n Front Immunol $x MED00181405
LZP    __
$a Pubmed-20230120

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace