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3 notes.
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49G2: 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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49G2: 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)
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49G2: 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, low for 2/11 strains; and high against 3 subtype B, medium against 3 subtype B of a standard panel of 27 HIV-1; potency against autologous viruses was negligible, low against virus from patient SUMA. MAb 49G2 had significant ADCC activity against cells infected with 3 of 3 lab strains and 4 of 5 T/F strains tested.
RamirezValdez2015
(ADCC, antibody generation, neutralization, binding affinity)
References
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3 references.
Isolation 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.
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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.
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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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