Found 1 matching record:
Displaying record number 1593
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MAb ID |
KD-247 |
HXB2 Location |
Env(311-315) DNA(7155..7169) |
Env Epitope Map
|
Author Location |
Env |
Research Contact |
Shuzo Matsushita, Kumamoto University, Japan shuzo@kaiju.medic.kumamoto-u.ac.jp |
Epitope |
IGPGR
|
Epitope Alignment
|
Subtype |
B |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
humanized mouse(IgG) |
Patient |
|
Immunogen |
engineered, vaccine |
Country |
Japan |
Keywords |
anti-idiotype, antibody binding site, antibody generation, antibody sequence, binding affinity, compensatory mutation, effector function, escape, glycosylation, immunoprophylaxis, immunotherapy, mimics, neutralization, review, structure, variant cross-reactivity, viral fitness and/or reversion |
Vaccine Details
Notes
Showing 14 of
14 notes.
-
KD-247: Passive application of KD-247 to patients with chronic asymptomatic HIV-1 infection reduced viral load.
Matsushita2015
(immunotherapy)
-
KD-247: Determined the crystal structure of KD-247 to reveal the interactions responsible for the antibody's B-clade-specific neutralization.
Kirby2015
(antibody sequence, structure)
-
KD-247: The cross-reactivity, neutralization, and ADCC activity of MAbs derived from a long-term non-progressive patient were analyzed to show complementary and synergistic neutralization by a set of mAbs is an effective substitute for induction of bNAbs; KD-247 was included as a control, where median neutralization potency against 5/11 laboratory and primary strains was high, between 0.05-10 µl; and high only against 1 subtype B of a standard panel of 27 HIV-1; potency against autologous virus was low. KD-247 had significant ADCC activity against cells infected with 3 of 3 lab strains and 3 of 5 T/F strains tested.
RamirezValdez2015
(effector function, neutralization)
-
KD-247: KD-247 can efficiently neutralize a broad panel of clade B, but not non-clade B, HIV-1 isolates. To overcome this limitation, purification protocols to recover, purify, and refold the KD-247 scFv from inclusion bodies were established. The refolded KD-247 scFv showed neutralizing activity against replication-competent HIV-1 BaL and JR-FL Env pseudotyped HIV-1, at potency comparable to that of the native full-size KD-247 antibody.
Ong2012
(neutralization)
-
KD-247: Although KD-247 targets the GPGR sequence at the V3 loop, not all GPGR-positive HIV-1 isolates are neutralized by KD-247. The potential mechanism of neutralization susceptibility was studied by searching for nonepitope neutralization regulatory (NNR) mutations that sensitize GPGR-bearing HIV-1AD8 to KD-247. Mutations specifically affected KD-247-, but not b12-mediated neutralization. Combined KD-247-sensitizing NNR mutations had an additive effect sensitizing the virus by up to 10,000 fold.
Takizawa2011
(neutralization, escape)
-
KD-247: Pretreatment by the small NBD-556 CD4-mimicking compound remarkably increased binding of KD-247 to JR-FL Env, indicating enhancement of KD-247 epitope accessibility by NBD-556. Combinations of KD-247 with the sCD4 and NBD-556 showed highly synergistic effects on the inhibitory concentrations. HIV-1 Pt.3 strain was completely resistant to neutralization by KD-247, but when pretreated with NBD-556, the virus became sensitive to neutralization by this Ab.
Yoshimura2010
(mimics, neutralization, binding affinity)
-
KD-247: Postinfection passive immunization of SHIV-infected monkeys with KD-247 resulted in suppressed viral loads and protection against loss of CD4+ T cells. The lymph nodes of monkeys given KD-247 maintained normal shape while those in monkeys given control IgG were atrophied. Thymuses of monkeys given KD-247 were hypertrophic while those in control monkeys were atrophied. Complete protection was not achieved. One of six monkeys given KD-247 could not maintain Ab concentrations, and binding of KD-247 to antigen peptides decreased by 60% after reaction with the plasma from this monkey, suggesting presence of anti-idiotype Abs.
Murakami2009
(anti-idiotype, binding affinity, immunotherapy)
-
KD-247: A review about the in vivo efficacy of KD-247 and other MAbs against HIV-1, and about inhibition of HIV-1 infection by Ab fragments Fab, scFv and engineered human Ab variable domains or "domain antibodies" (dAbs).
Chen2009b
(neutralization, immunotherapy, review)
-
KD-247: Neutralization evading mutants were obtained by selection of HIV-1 BaL with KD-247. In the presence of low Ab concentrations, viruses with mutations in C2 (T240S and I283T) and V3 (T319A) showed moderate resistance to neutralization by KD-247. In the presence of high concentrations of KD-247 viruses with PNGS in the V2 region and C2 mutation T240S and V3 mutations R315K and F317L were observed. Viruses with both the V2 PNGS and mutations in V3 were highly resistant to KD-247 while viruses with V3 mutations alone were less resistant, indicating that glycosylation in V2 contributed to neutralization resistance. Insertion of the V2 PNGS (potential N-linked glycosylation site) and the mutation in the V3 tip R315K caused a fitness loss which was compensated by the V3 F317L and C2 T240S mutations. After acquisition of the compensatory mutations, the resistant HIV-1 variants did not revert back to wildtype in the absence of Ab.
Hatada2010
(compensatory mutation, glycosylation, neutralization, viral fitness and/or reversion, escape)
-
KD-247: An escape variant highly resistant to KD-247 was induced with a mutation G314E in the V3 tip of gp120. This mutant virus was shown to be sensitive to CCR5 inhibitors, RANTES, rsCD4 and an anti-CCR5 MAb, but resistant to an anti-CD4 MAb. Combinations of this Ab and CCR5 inhibitors were found to be highly synergistic.
Yoshimura2006
(escape)
-
KD-247: The epitope recognized by this MAb was mapped to IGPGRA. The arginine (R) could not be replaced by any other amino acid, while the amino acids in the flanking sequence, IG, could be substituted without loss of KD-247 binding. The neutralizing sensitivity of clade B SF162, 89.6 and JR-FL to this Ab varied although they share the IGPGRA sequence. At high concentrations, KD-247 was able to suppress replication of viruses derived from patients. At lower concentrations of the MAb, viral replication continued and neutralization escape variants emerged. The escaped viruses had either igpgGa or igpgSa sequences at the tip of the V3 loop.
Matsushita2005
(antibody binding site, neutralization, escape)
-
KD-247: This Ab was shown to efficiently neutralize clade B and B' CXCR4 and CCR5 HIV-1 primary isolates with matching V3 sequence motifs while it did not neutralize sequence-mismatched clade B and E isolates. It was also shown to provide sterile protection against SHIV challenge when passively transferred to monkeys in a single high dose. Lower doses provided partial protection.
Eda2006
(immunoprophylaxis, variant cross-reactivity)
-
KD-247: Escape variants were induced by exposing the HIV-1 strain MOKW to different concentrations of KD-247 in vitro. In the presence of relatively low concentrations of the Ab, viral variants with V2 mutations R166K and D167N were found with partial resistance against KD-247. In the presence of high concentrations of KD-247, in addition to the V2 mutations, a V3 tip mutation (P313L) induced complete resistance to KD-247. V2 P175L substitution conferred high resistance to KD-247, however, additional KN substitutions in positions 166 and 167 resulted in a less resistant virus with a replication advantage.
Shibata2007
(antibody binding site, variant cross-reactivity, escape, binding affinity)
-
KD-247: A new humanize MAb recognizing the V3 tip sequence was generated by transferring the genes of the complementary determining region of the mouse NAb C25 into genes of a human V region. C25 was raised by serial vaccinations of a mouse with distinctive six B clade V3 loop peptides. KD-247 was shown to neutralize laboratory and primary isolates of CXCR4 and CCR5 viruses that possess a GPGR sequence in the Env V3 tip region more effectively than any of the reference Abs used in the study. KD-247 was shown to recognize the narrow V3 tip sequence with high affinity.
Eda2006a
(antibody binding site, antibody generation, variant cross-reactivity, binding affinity, antibody sequence)
References
Showing 14 of
14 references.
Isolation Paper
Eda2006a
Yasuyuki Eda, Mari Takizawa, Toshio Murakami, Hiroaki Maeda, Kazuhiko Kimachi, Hiroshi Yonemura, Satoshi Koyanagi, Kouichi Shiosaki, Hirofumi Higuchi, Keiichi Makizumi, Toshihiro Nakashima, Kiyoshi Osatomi, Sachio Tokiyoshi, Shuzo Matsushita, Naoki Yamamoto, and Mitsuo Honda. Sequential Immunization with V3 Peptides from Primary Human Immunodeficiency Virus Type 1 Produces Cross-Neutralizing Antibodies against Primary Isolates with a Matching Narrow-Neutralization Sequence Motif. J. Virol., 80(11):5552-5562, Jun 2006. PubMed ID: 16699036.
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Chen2009b
Weizao Chen and Dimiter S. Dimitrov. Human Monoclonal Antibodies and Engineered Antibody Domains as HIV-1 Entry Inhibitors. Curr. Opin. HIV AIDS, 4(2):112-117, Mar 2009. PubMed ID: 19339949.
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Eda2006
Yasuyuki Eda, Toshio Murakami, Yasushi Ami, Tadashi Nakasone, Mari Takizawa, Kenji Someya, Masahiko Kaizu, Yasuyuki Izumi, Naoto Yoshino, Shuzo Matsushita, Hirofumi Higuchi, Hajime Matsui, Katsuaki Shinohara, Hiroaki Takeuchi, Yoshio Koyanagi, Naoki Yamamoto, and Mitsuo Honda. Anti-V3 Humanized Antibody KD-247 Effectively Suppresses Ex Vivo Generation of Human Immunodeficiency Virus Type 1 and Affords Sterile Protection of Monkeys against a Heterologous Simian/Human Immunodeficiency Virus Infection. J. Virol., 80(11):5563-5570, Jun 2006. PubMed ID: 16699037.
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Hatada2010
Makiko Hatada, Kazuhisa Yoshimura, Shigeyoshi Harada, Yoko Kawanami, Junji Shibata, and Shuzo Matsushita. Human Immunodeficiency Virus Type 1 Evasion of a Neutralizing Anti-V3 Antibody Involves Acquisition of a Potential Glycosylation Site in V2. J. Gen. Virol., 91(Pt 5):1335-1345, May 2010. PubMed ID: 20032207.
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Kirby2015
Karen A. Kirby, Yee Tsuey Ong, Atsuko Hachiya, Thomas G. Laughlin, Leslie A. Chiang, Yun Pan, Jennifer .L Moran, Bruno Marchand, Kamalendra Singh, Fabio Gallazzi, Thomas P. Quinn, Kazuhisa Yoshimura, Toshio Murakami, Shuzo Matsushita, and Stefan G. Sarafianos. Structural Basis of Clade-Specific HIV-1 Neutralization by Humanized Anti-V3 Monoclonal Antibody KD-247. FASEB J., 29(1):70-80, Jan 2015. PubMed ID: 25351987.
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Matsushita2005
Shuzo Matsushita, Soichiro Takahama, Junji Shibata, Tetsuya Kimura, Koichi Shiozaki, Yasuyuki Eda, Atsushi Koito, Toshio Murakami, and Kazuhisa Yoshimura. Ex Vivo Neutralization of HIV-1 Quasi-Species by a Broadly Reactive Humanized Monoclonal Antibody KD-247. Hum. Antibodies, 14(3-4):81-88, 2005. PubMed ID: 16720978.
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Matsushita2015
Shuzo Matsushita, Kazuhisa Yoshimura, Kristel Paola Ramirez, Jaya Pisupati, Toshio Murakami, and KD-1002 Study Group. Passive Transfer of Neutralizing mAb KD-247 Reduces Plasma Viral Load in Patients Chronically Infected with HIV-1. AIDS, 29(4):453-462, 20 Feb 2015. PubMed ID: 25630040.
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Murakami2009
Toshio Murakami, Yasuyuki Eda, Tadashi Nakasone, Yasushi Ami, Kenji Someya, Naoto Yoshino, Masahiko Kaizu, Yasuyuki Izumi, Hajime Matsui, Katsuaki Shinohara, Naoki Yamamoto, and Mitsuo Honda. Postinfection Passive Transfer of KD-247 Protects against Simian/Human Immunodeficiency Virus-Induced CD4+ T-Cell Loss in Macaque Lymphoid Tissue. AIDS, 23(12):1485-1494, 31 Jul 2009. PubMed ID: 19528788.
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Ong2012
Y. T. Ong, K. A. Kirby, A. Hachiya, L. A. Chiang, B. Marchand, K. Yoshimura, T. Murakami, K. Singh, S. Matsushita, and S. G. Sarafianos. Preparation of Biologically Active Single-Chain Variable Antibody Fragments That Target the HIV-1 gp120 V3 Loop. Cell. Mol. Biol. (Noisy-le-grand), 58(1):71-79, 2012. PubMed ID: 23273194.
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RamirezValdez2015
Kristel Paola Ramirez Valdez, Takeo Kuwata, Yasuhiro Maruta, Kazuki Tanaka, Muntasir Alam, Kazuhisa Yoshimura, and Shuzo Matsushita. Complementary and Synergistic Activities of Anti-V3, CD4bs and CD4i Antibodies Derived from a Single Individual Can Cover a Wide Range of HIV-1 Strains. Virology, 475:187-203, 15 Jan 2015. PubMed ID: 25486586.
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Shibata2007
Junji Shibata, Kazuhisa Yoshimura, Akiko Honda, Atsushi Koito, Toshio Murakami, and Shuzo Matsushita. Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 81(8):3757-3768, Apr 2007. PubMed ID: 17251298.
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Takizawa2011
Mari Takizawa, Kosuke Miyauchi, Emiko Urano, Shigeru Kusagawa, Katsuhiko Kitamura, Satoshi Naganawa, Toshio Murakami, Mitsuo Honda, Naoki Yamamoto, and Jun Komano. Regulation of the Susceptibility of HIV-1 to a Neutralizing Antibody KD-247 by Nonepitope Mutations Distant from its Epitope. AIDS, 25(18):2209-2216, 28 Nov 2011. PubMed ID: 21866041.
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Yoshimura2006
Kazuhisa Yoshimura, Junji Shibata, Tetsuya Kimura, Akiko Honda, Yosuke Maeda, Atsushi Koito, Toshio Murakami, Hiroaki Mitsuya, and Shuzo Matsushita. Resistance Profile of a Neutralizing Anti-HIV Monoclonal Antibody, KD-247, that Shows Favourable Synergism with Anti-CCR5 Inhibitors. AIDS, 20(16):2065-2073, 24 Oct 2006. PubMed ID: 17053352.
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Yoshimura2010
Kazuhisa Yoshimura, Shigeyoshi Harada, Junji Shibata, Makiko Hatada, Yuko Yamada, Chihiro Ochiai, Hirokazu Tamamura, and Shuzo Matsushita. Enhanced Exposure of Human Immunodeficiency Virus Type 1 Primary Isolate Neutralization Epitopes through Binding of CD4 Mimetic Compounds. J. Virol., 84(15):7558-7568, Aug 2010. PubMed ID: 20504942.
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