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Displaying record number 2477

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MAb ID	4E9C
HXB2 Location	Env	Env Epitope Map
Author Location	gp120
Epitope
Subtype	B
Ab Type	gp120 CD4i
Neutralizing	L View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG1κ)
Patient	KTS376
Immunogen	HIV-1 infection
Country	Japan
Keywords	ADCC, antibody binding site, antibody generation, antibody interactions, binding affinity, drug resistance, mimics, neutralization, subtype comparisons

Notes

Showing 6 of 6 notes.

4E9C: Single chain variable fragments (scFvs) were constructed for mAbs 916B2, 4E9C, and 25C4b. Coverage of neutralization by the scFvs against a panel of 66 multiclade pseudoviruses was 89% for 4E9C, 95% for 25C4b, and 100% for 916B2. 25C4b bound the region spanning multiple domains of hairpin 1 (H1) and H2 of the bridging sheet and V3 base, similar to mAb 17b. For 4E9C, V3-base dependent binding was apparent based on lack of binding to mutants containing a V3 truncation. In contrast, binding of 916B2 was dependent on the H1 region. It was noted that 4E9C and 12G10 belong to the same clonal lineage. Tanaka2017 (antibody binding site, neutralization)
4E9C: The study compared well-characterized nAbs (2G12, b12, VRC01, 10E8, 17b) with 4 mAbs derived from a Japanese patient (4E9C, 49G2, 916B2, 917B11), in their neutralization and ADCC activity against viruses of subtypes B and CRF01. CRF01 viruses were less susceptible to neutralization by 2G12 and b12, while VRC01 was highly effective in neutralizing CRF01 viruses. 49G2 showed better neutralization breadth against CRF01 than against B viruses. CRF01_AE viruses from Japan also showed a slightly higher susceptibility to anti-CD4i Ab 4E9C than the subtype B viruses, and to CRF01_AE viruses from Vietnam. Neutralization breadth of other anti-CD4i Abs 17b, 916B2 and 917B11 was low against both subtype B and CRF01_AE viruses. Anti-CD4bs Ab 49G2, which neutralized only 22% of the viruses, showed the broadest coverage of Fc-mediated signaling activity against the same panel of Env clones among the Abs tested. The CRF01_AE viruses from Japan were more susceptible to 49G2-mediated neutralization than the CRF01_AE viruses from Vietnam, but Fc-mediated signaling activity of 49G2was broader and stronger in the CRF01_AE viruses from Vietnam than the CRF01_AE viruses from Japan. Thida2019 (ADCC, neutralization, subtype comparisons)
4E9C: MAb 1E5 was isolated from a patient infected with CRF02_AG, and both the IGg1 and IGg3 forms were produced. Its binding region was determined to be the C1-C2 region of gp120. In a binding competition assay, 1E5 enhanced rather than competed for A32 binding, suggesting that the 1E5 epitope does not overlap with the A32 epitope. Neither the IgG1 nor the IgG3 forms of 1E5 showed any neutralization activity, similar to the other C1C2 antibodies. Both IgG1 and IgG3 forms of 1E5 showed low ADCC activity against most of the strains, although 1E5-IgG3 showed higher ADCC activity than 1E5-IgG1. 1E5 ADCC activity was enhanced in the presence of A32, 4E9C, and anti-CoRBS antibodies. The 1E5 antibody sequence and germline gene usage were determined. MdZahid2021 (ADCC, antibody interactions)
4E9C: Cells lines containing HIV from patient KK were passaged in the presence of ceniciviroc (CVC) to derive CVC-resistant strains. These strains were sensitive to antibodies, including 0.5γ, 4E9C, and 49G2. Resistance to 0.5γ and 4E9C was caused by novel substitutions R315K, G324R, and E381K. These loci occur near substitutions conferring resistance to CVC, and these changes are associated with a reversion to a CVC-sensitive phenotype. These results suggest that CVC and NAbs may restrict the emergence of variants resistant to each other. Kuwata2016 (drug resistance, neutralization)
4E9C: B-cell clones derived from a long-term non-progressive patient were selected for MAbs reactive to gp120. These MAbs bound to several complementary regions of gp120 and synergistically neutralized a wide range of HIV subtypes. This could be an alternative method to induction of bNAbs. Median neutralization potency against 4/11 laboratory and primary strains was high, between 0.05-10 µl; and medium against 3 subtype B, 2 subtype C of a standard panel of 27 HIV-1; potency against autologous virus was negligible. MAb 4E9C had significant ADCC activity against cells infected with 3 of 3 lab strains and 3 of 5 T/F strains tested. RamirezValdez2015 (ADCC, neutralization, binding affinity)
4E9C: MAbs were established from a patient with long-term nonprogressive illness. B cells from the patient’s PBMC were transformed by Epstein-Barr virus, followed by cloning. HIV-1 Pt.3 strain was completely resistant to neutralization by 4E9C, but when pretreated with the small CD4-mimicking compound NBD-556, the virus became sensitive to neutralization by this Ab. Yoshimura2010 (antibody generation, mimics, neutralization)

References

Showing 6 of 6 references.

Isolation Paper
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. Show all entries for this paper.

Kuwata2016 Takeo Kuwata, Ikumi Enomoto, Masanori Baba, and Shuzo Matsushita. Incompatible Natures of the HIV-1 Envelope in Resistance to the CCR5 Antagonist Cenicriviroc and to Neutralizing Antibodies. Antimicrob. Agents Chemother., 60(1):437-450, 2 Nov 2015. PubMed ID: 26525792. Show all entries for this paper.

MdZahid2021 Hasan Md Zahid, Takeo Kuwata, Shokichi Takahama, Yu Kaku, Shashwata Biswas, Kaho Matsumoto, Hirokazu Tamamura, and Shuzo Matsushita. Functional analysis of a monoclonal antibody reactive against the C1C2 of Env obtained from a patient infected with HIV-1 CRF02_AG. Retrovirology, 18(1):23 doi, Aug 2021. PubMed ID: 34419098 Show all entries for this paper.

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. Show all entries for this paper.

Tanaka2017 Kazuki Tanaka, Takeo Kuwata, Muntasir Alam, Gilad Kaplan, Shokichi Takahama, Kristel Paola Ramirez Valdez, Anna Roitburd-Berman, Jonathan M. Gershoni, and Shuzo Matsushita. Unique binding modes for the broad neutralizing activity of single-chain variable fragments (scFv) targeting CD4-induced epitopes. Retrovirology, 14(1):44 doi, Sep 2017. PubMed ID: 28938888 Show all entries for this paper.

Thida2019 Win Thida, Takeo Kuwata, Yosuke Maeda, Tetsu Yamashiro, Giang Van Tran, Kinh Van Nguyen, Masafumi Takiguchi, Hiroyuki Gatanaga, Kazuki Tanaka, and Shuzo Matsushita. The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses. Biochem Biophys Res Commun, 508(1):46-51 doi, Jan 2019. PubMed ID: 30470571 Show all entries for this paper.