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Displaying record number 3291
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MAb ID |
CH235.9 (CH493, CH235.09) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env |
Epitope |
|
Subtype |
C |
Ab Type |
gp120 CD4BS |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human |
Patient |
Donor CH505 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, binding affinity, broad neutralizer, escape, mutation acquisition, neutralization, review, structure |
Notes
Showing 4 of
4 notes.
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CH235.09: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. bNAbs with >25% breadth of neutralization belonged to 20 classes of antibody with a large number of protruding loops and somatic hypermutation (SHM). HIV epitopes recognized placed the bNAbs into 6 categories (viz. V1V2, Glycan-V3, CD4-binding site, Silent face center, Fusion peptide and Subunit Interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. CH235.9-Env formed a distinct group within the CD4bs category, Class 8ANC131. Crystal structure data for VH1-46 germline-derived bNAb CH235.9 complexed to HIV-1 Clade A/E 93TH057 gp120 was found in PDB ID: 5F9O.
Chuang2019
(antibody binding site, antibody interactions, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
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CH235.9: This review discussed antibody-virus coevolution and lineage development as a path to elicit broadly neutralizing Abs. CD4bs mAbs from donor CH505 (lineages CH103 and CH235) were used as main examples.
Bonsignori2017a
(review, antibody lineage)
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This patent application states that CH493 is also referred to as CH235.9.
Lam2017
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CH235.9: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's VL and VH chains at 17 timepoints in the donor's infection. Two of these had greater neutralization potency, CH235.9 and CH235.12. Study of crystal structures indicated a site of vulnerability near the Env CD4 binding site. The lineages of CH103 and CH235, both derived from Donor CH505 were compared - CH103 lineage Kd increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower Kds and Kas over maturation. This mAb was autoreactive, at the cytoplasmic level. CH235.9 CDRL3 interacts with HIV-1 N280 in gp120, forming 3 H-bonds which are proposed to be disrupted due to autologous virus escape mutations in patient CH505, N280S and N280T. CH235.9 was produced as a recombinant mAb of VH and VL sequences found at week 152. CH235.9 neutralized 44% of a 75-autologous virus panel, 77% of a 202-multiclade Env-psuedovirus panel and 58% of an 113-patient CH505-derived autologous pseudoviral panel as part of CH235 lineages, all at potencies of <50 µg/ml. It also acquired the ability to neutralize all loop D mutants that were resistant to early members of the CH235 lineage.
Bonsignori2016
(antibody generation, mutation acquisition, neutralization, escape, binding affinity, antibody sequence, antibody lineage)
References
Showing 4 of
4 references.
Isolation Paper
Bonsignori2016
Mattia Bonsignori, Tongqing Zhou, Zizhang Sheng, Lei Chen, Feng Gao, M. Gordon Joyce, Gabriel Ozorowski, Gwo-Yu Chuang, Chaim A. Schramm, Kevin Wiehe, S. Munir Alam, Todd Bradley, Morgan A. Gladden, Kwan-Ki Hwang, Sheelah Iyengar, Amit Kumar, Xiaozhi Lu, Kan Luo, Michael C. Mangiapani, Robert J. Parks, Hongshuo Song, Priyamvada Acharya, Robert T. Bailer, Allen Cao, Aliaksandr Druz, Ivelin S. Georgiev, Young D. Kwon, Mark K. Louder, Baoshan Zhang, Anqi Zheng, Brenna J. Hill, Rui Kong, Cinque Soto, NISC Comparative Sequencing Program, James C. Mullikin, Daniel C. Douek, David C. Montefiori, Michael A. Moody, George M. Shaw, Beatrice H. Hahn, Garnett Kelsoe, Peter T. Hraber, Bette T. Korber, Scott D. Boyd, Andrew Z. Fire, Thomas B. Kepler, Lawrence Shapiro, Andrew B. Ward, John R. Mascola, Hua-Xin Liao, Peter D. Kwong, and Barton F. Haynes. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell, 165(2):449-463, 7 Apr 2016. PubMed ID: 26949186.
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Bonsignori2017a
Mattia Bonsignori, Hua-Xin Liao, Feng Gao, Wilton B. Williams, S. Munir Alam, David C. Montefiori, and Barton F. Haynes. Antibody-Virus Co-evolution in HIV Infection: Paths for HIV Vaccine Development. Immunol. Rev., 275(1):145-160, Jan 2017. PubMed ID: 28133802.
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Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
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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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