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6 total notes.
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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)
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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)
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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)
References
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6 total references.
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
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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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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
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