Found 1 matching record:
Displaying record number 3651
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MAb ID |
DH270.4 (DH429) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Epitope |
|
Subtype |
C |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P (tier 2) View neutralization details |
Species
(Isotype)
|
human(IgG) |
Patient |
CH848 |
Immunogen |
HIV-1 infection |
Country |
Malawi |
Keywords |
acute/early infection, antibody binding site, antibody generation, antibody lineage, antibody sequence, autologous responses, binding affinity, broad neutralizer, germline, mother-to-infant transmission, neutralization, structure, transmission pair |
Notes
Showing 3 of
3 notes.
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DH270.4: HIV-1 env genes were sequenced from 16 mother/infant transmitting pairs. Infant transmitted-founder (T/F) and representative maternal non-transmitted Env variants were identified and used to generate pseudoviruses for paired maternal plasma neutralization analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma, while all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies (2G12, CH01, PG9, PG16, PGT121, PGT126, DH429, b12, VRC01, NIH45-46, CH31, 4E10, 2F5, 10E8, DH512) and variably sensitive to heterologous plasma neutralizing antibodies. Antibody mixture CH01/31 was used as a positive control for neutralization. The infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants. These findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could reduce infant HIV-1 infection risk.
Kumar2018
(neutralization, acute/early infection, mother-to-infant transmission, transmission pair)
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This patent application states that DH429 is also referred to as DH270.4.
Lam2017
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DH270.4: The study isolated 3 new V3-glycan antibody lineages (DH270, DH272, DH475) from donor CH848, who was followed for 5 years starting from the time of transmission. The DH272 and DH475 lineages had neutralization patterns that likely selected for observed viral escape variants, which, in turn, stimulated the DH270 lineage to potent neutralization breadth. DH270 antibodies were recovered from memory B cells at all three sampling times (weeks 205, 232, and 234 post-infection). Clonal expansion occurred at week 186, concurrent with the development of plasma neutralization breadth. Like some previously-characterized Abs (PGT121, PGT128, 10-1074), the DH270 lineage mAbs bound to Env N332, and their neutralization was reduced or abrogated by mutation of this residue. DH270.4 had broad autologous neutralizing activity and was unique among the mature DH270 lineage mAbs in being able to neutralize autologous viruses isolated during the first year of infection. MAb DH270.4, isolated from cultured memory cells collected 232 weeks after transmission that bound to consensus C gp120 but not consensus C gp120 N332A, neutralized 16/24 heterologous pseudoviruses with IC50 <50 μg/ml. Compared to unmutated common ancestor (UCA), DH270.4 had 28 (22.0%) and 16 (14.5%) aa substitutions in heavy and light chains, respectively.
Bonsignori2017
(antibody binding site, antibody generation, autologous responses, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer, germline)
References
Showing 3 of
3 references.
Isolation Paper
Bonsignori2017
Mattia Bonsignori, Edward F. Kreider, Daniela Fera, R. Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S. Munir Alam, Baptiste Aussedat, William E. Walkowicz, Kwan-Ki Hwang, Kevin O. Saunders, Ruijun Zhang, Morgan A. Gladden, Anthony Monroe, Amit Kumar, Shi-Mao Xia, Melissa Cooper, Mark K. Louder, Krisha McKee, Robert T. Bailer, Brendan W. Pier, Claudia A. Jette, Garnett Kelsoe, Wilton B. Williams, Lynn Morris, John Kappes, Kshitij Wagh, Gift Kamanga, Myron S. Cohen, Peter T. Hraber, David C. Montefiori, Ashley Trama, Hua-Xin Liao, Thomas B. Kepler, M. Anthony Moody, Feng Gao, Samuel J. Danishefsky, John R. Mascola, George M. Shaw, Beatrice H. Hahn, Stephen C. Harrison, Bette T. Korber, and Barton F. Haynes. Staged Induction of HIV-1 Glycan-Dependent Broadly Neutralizing Antibodies. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298420.
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Kumar2018
Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, and Sallie R. Permar. Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission Are Neutralization Resistant to Paired Maternal Plasma. PLoS Pathog., 14(4):e1006944, Apr 2018. PubMed ID: 29672607.
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Lam2017
C. Y. K. Lam, J. L. Nordstrom, B. F. Haynes, and M. Bonsignori. Bispecific Molecules Comprising an HIV-1 Envelope Targeting Arm. WIPO patent application, Jan 2017. URL: https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017011414. Application number: PCT/US2016/041809.
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