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MAb ID	CH103
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Subtype	C
Ab Type	gp120 CD4BS
Neutralizing	P View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG1)
Patient	Donor CH505
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chimeric antibody, computational epitope prediction, escape, glycosylation, neutralization, polyclonal antibodies, review, structure, vaccine antigen design, vaccine-induced immune responses

Notes

Showing 35 of 35 notes.

CH103: 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. CH103-Env formed a distinct group within the CD4bs category, Class CH103. Crystal structure data for bNAb CH103 complexed to HIV-1 gp120 was found in PDB ID: 4JAN. Chuang2019 (antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
CH103: In an attempt to engage appropriate germline B cells that give rise to bNAbs, a combination of Env glycan modifications that permit far greater neutralization potency by near germline forms of multiple VRC01-class bNAbs were tested. The authors assessed CD4bs bNAbs for neutralizing activity against of Env-pseudotyped viruses (EPV) that were either Man5-enrichment and/or had targeted glycan deletion and concluded that neutralization by germline-reverted forms of VRC01-class bNAbs requires a combination of both Man5-enrichment and glycan deletion. In particular, Man5-enrichment increased the sensitivity of 426c by 8–12 fold when assayed with mature VRC01, 3BNC117, VRC-CH31 and CH103, and this sensitivity increased further by targeted glycan deletion. Furthermore, Man5-enrichment increased the sensitivity of subtype C transmitted-founder 426c EPV that lacked glycan N276, and those that lacked two glycans at N460 and N463, to mature VRC01 by ˜10-fold. LaBranche2018 (antibody interactions, antibody lineage)
CH103: This study looks at the role of somatic mutations within antibody variable and framework regions (FWR) in bNAbs and how these mutations alter thermostability and neutralization as the Ab lineage reaches maturation. The emergence and selection of different mutations in the complementarity-determining and framework regions are necessary to maintain a balance between antibody function and stability. The study shows that all major classes of bnAbs (DH2070, CH103, CH235 etc.) have lower thermostability than their corresponding inferred UCA antibodies. Mutations in the CH103 UCA show that the mutants have lower thermostability and stronger neutralization. Henderson2019 (neutralization, antibody lineage, broad neutralizer)
CH103: This study demonstrated that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens eliciting Ab responses with greater neutralization breadth. Data from four large virus panels were used to comprehensively map viral signatures associated with bNAb sensitivity, hypervariable region characteristics, and clade effects. The bNAb signatures defined for the V2 epitope region were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine which resulted in increased breadth of NAb responses compared with Env 459C alone. CH103 which resulted in increased breadth of NAb responses compared with Env 459C alone Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
CH103: This review discusses current HIV bNAb immunogen design strategies, recent progress made in the development of animal models to evaluate potential vaccine candidates, advances in the technology to analyze antibody responses, and emerging concepts in understanding B cell developmental pathways that may facilitate HIV vaccine design strategies. Andrabi2018 (vaccine antigen design, review)
CH103: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. CH103 is polyreactive, but not autoreactive. Liu2015a (autoantibody or autoimmunity, antibody polyreactivity)
CH103: This study reports host tolerance mechanisms that limit the development of CD4bs and HCDR3-binder bNAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs bnAbs recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env+ B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing. Stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development. The crystal structure revealed that CH103 footprint rests heavily on the CD4-binding loop and V5. Immune tolerance in CH103 germ line knock-in mice showed reduced total B cell numbers and frequencies of follicular mature B cells. In CH103 KI mice, a large proportion of Abs used a similar VH , but different VL than did the CH103 UCA, showing that receptor editing 36 was one host tolerance mechanism limiting development of CD4-binding site HCDR3-binder bnAbs. Williams2017a (glycosylation, structure, antibody lineage, chimeric antibody)
CH103: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies. Zhou2017 (glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
CH103: 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)
CH103: This review summarizes vaccine approaches to counter HIV diversity. A structural map illustrated the contact regions of several bNAbs: VRC26.09, PGT128, CH235.12, and 10E8. Structures illustrating the bNAbs' tolerance for sequence variation were illustrated for CH235.12, PGT128, VRC26.09, and 10E8. CD4BS bNAbs such as VRC01 and CH235.12 illustrate that bNAbs bind to both conserved and hypervariable regions of Env. Donor CH505 initially developed mAb lineage CH103; its maturation was facilitated by escape mutants, which were selected by early antibodies in the CH235 lineage, illustrating lineage cooperation. Korber2017 (antibody binding site, vaccine antigen design, review)
CH103: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. CH58 was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity. Bradley2016a (neutralization)
CH103: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. VRC01 was 1 of 4 reference VRC01-like bNAbs - VRC01, 3BNC117, 8ANC131, CH103. Crooks2015 (glycosylation, neutralization)
CH103: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016. Wu2016 (review)
CH103: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195). Stewart-Jones2016 (antibody binding site, glycosylation, structure)
CH103: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed. Burton2016 (review, structure)
CH103: This study estimated intra-lineage longitudinal evolutionary rate changes for the VRC26 and CH103 lineages and compared these to the reported rate changes of the VRC01 lineage. Results confirmed that a decreasing evolutionary rate is common to all three lineages. Sheng2016 (antibody lineage)
CH103: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among CD4bs binding bNAbs, CH103 recognizes trimer similarly to 1NC9, CH106, 3BNC117 and VRC01, and is inhibited by sCD4. CH103 enhanced binding of several V1/V2-glycan, V3-glycan or outer domain (OD)-glycan bNAbs. Derking2015 (antibody interactions, neutralization, binding affinity, structure)
CH103: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 13/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting CH103 binding to CD4bs, but gp140-immunized sera could not. 4/4 similarly trimer-immunized macaque sera also inhibited CH103 binding. Serum inhibition of CH103-trimer binding significantly correlated with rabbit autologous neutralization of the trimer-equivalent psuedovirus, BG505.T332N. Sanders2015 (antibody generation, neutralization, binding affinity, polyclonal antibodies)
CH103: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb CH103 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too. Sanders2013 (assay or method development, neutralization, binding affinity)
CH103: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. CD4bs-binding gl-CH103 precursor bound to 1/3 trimers, ZM197M. Sliepen2015 (binding affinity, antibody lineage)
CH103: Donor EB179 was a long-term non-progressor with high serum neutralization breadth and potency. 8 B-cell clones produced antibodies of which 179NC75 had the highest neutralization, especially to Clade B virus, neutralizing 70% of a clade-B pseudovirus panel and 6 out of 9 cross-clade Env pseudoviruses. When compared to other CD4bs bNAbs against a panel of 22 Tier-2 clade B viruses, 179NC75 was more potent than CH103 against 6 viruses. Freund2015 (neutralization, broad neutralizer)
CH103: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's V_L and V_H 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 K_d increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower K_ds and K_as over maturation. CH103, a CDR H3-dependent CD4bs bnAb, neutralized 100% of an 113-patient CH505-derived autologous pseudoviral panel as part of CH103 lineages, at a potency of <50 µg/ml. It binds BG505 of Env with a stoichiometry of 3. Bonsignori2016 (neutralization, binding affinity, antibody sequence, antibody lineage)
CH103: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers. deTaeye2015 (antibody binding site)
CH103: This study isolated 4 novel antibodies that bind the CD4 binding site of Env. Population-level analysis classified a diverse group of CD4bs antibodies into two types: CDR H3-dominated or VH-gene-restricted, each with distinct ontogenies. Structural data revealed that neutralization breadth was correlated with angle of approach of the antibodies to the CD4 binding region. CH103 was one of the antibodies in the CDR H3-dominated class. Zhou2015 (neutralization, structure, antibody lineage, broad neutralizer)
CH103: CD4-binding site Abs are reviewed. New insights from donor-serum responses, atomic-level structures of antibody-Env complexes, and next-generation sequencing of B-cell transcripts are invigorating vaccine-design efforts to elicit effective CD4-binding site Abs. Analysis of the epitopes recognized by CD4-binding Abs reveals substantial similarity in the recognized region of gp120. CH103 have been shown to utilize a different mode of recognition, with next-generation sequencing of both virus and antibody suggesting co-evolution to drive the development of antibody-neutralization breadth. Georgiev2013a (review)
CH103: A computational method, LASSIE (Longitudinal Antigenic Sequences and Sites from Intrahost Evolution), uses transmitted founder loss to identify virus hot-spots under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. Sequences and antibodies from patient CH505 were used to demonstrate the methodology. The neutralization of CH103, members of its clonal lineage (CH104, CH105, CH106), and its ancestral antibodies (IA1 - IA8 and UCA) were assayed against longitudinal Env sequences from patient CH505. Neutralization and binding assay results confirmed that selected viruses exhibited diverse antibody sensitivities, which increased with maturation of the bnAb lineage and generally followed the progression of mutations away from the TF virus. CH103 neutralized 100% of a panel of autologous env gp160s at IC₅₀ <50 µg/ml. Hraber2015 (neutralization, antibody lineage)
CH103: The IGHV region is central to Ag binding and consists of 48 functional genes. IGHV repertoire of 28 HIV-infected South African women, 13 of whom developed bNAbs, was sequenced. Novel IGHV repertoires were reported, including 85 entirely novel sequences and 38 sequences that matched rearranged sequences in non-IMGT databases. There were no significant differences in germline IGHV repertoires between individuals who do and do not develop bNAbs. IGHV gene usage of multiple well known HIV-1 bNAbs was also analyzed and 14 instances were identified where the novel non-IMGT alleles identified in this study, provided the same or a better match than their currently defined IMGT allele. For CH103 the published IMGT predicted allele was IGHV4-59*01 and alternate allele predicted from IGHV alleles in 28 South African individuals was IGHV4-59*1m2, with T94C nucleotide and Y32H amino acid change. Scheepers2015 (antibody lineage)
CH103: This study examined the development and co-evolution of autologous antibodies and viruses in two patients. Antibodies with limited heterologous breadth were able to potently neutralize autologous viruses, and such antibodies could select for neutralization-resistant autologous viruses implicated in transmission. The clonal lineages were compared to the CH103 clonal lineage derived from subject CH505. Moody2015 (neutralization)
CH103: Structures of progenitor and intermediate antibodies to CH103 lineage were analyzed. The critical feature of affinity maturation in the CH103 lineage was shown to be a small but significant shift in the relative orientations of VH and VL domains. The mutations leading to the conformational shift probably occurred in response to insertions into V5 in gp120 of autologous viruses, illustrating a mechanism of affinity maturation through mutation outside the Ag combining site. Structure of CH103/gp120 complex revealed a contact dominated by CDRH3. Fera2014 (neutralization, escape, structure, antibody lineage)
CH103: Advances (newly discovered Env targeting antibodies, CTL-control of infection, correlates of transmission risk, co-evolution of Env with bNAb, immunogens that overcome CTL epitope diversity) and promising approaches for HIV-1 vaccines were reviewed. CH103 lineage co-evolution with HIV-1 Env was discussed. Haynes2014 (neutralization, review)
CH103: This comment points out that Gao2013 et al. have uncovered an intermediate stage in the process of bnAb production. Viral escape from one B cell lineage, CH235, seen as mutations in the CD4bs D-loop, is then followed by emergence of the bnAb CH103 and its members (CH104, CH105, CH106), that not only bind those D-loop variants but also demonstrate broad cross-reactivity and neutralization potency. McHeyzer-Williams2014 (review)
CH103: As compared to early mutations in V- and CD4-binding loops that result in escape from antibody CH103, mutations in patient CH505's HIV-1 Env loop D generated a virus variant that showed 4.5 fold increased binding to and neutralizaton by bnAb CH103. The Env loop D mutations were driven by an independent antibody from a separate B-lineage, CH235. Thus, co-operation between 2 different B cell lineages in early infection induced potent, cross-reactive bnAb CH103 development. D loop mutants M11, M7, M8, M9, M20 and M21 however neutralized 10 fold better by CH103 over CH235. Gao2014 (antibody generation, neutralization, binding affinity, broad neutralizer)
CH103: This is a review of identified bNAbs, including the ontogeny of B cells that give rise to these antibodies. Breadth and magnitude of neutralization, unique features and similar bNAbs are listed. CH103 is a CD4bs Ab, with breadth 34%, IC₅₀ 8 μg per ml, and its unique feature is CDR H3 mode of recognition and reasonable affinity maturation. Kwong2013 (review)
CH103: A computational method to predict Ab epitopes at the residue level, based on structure and neutralization panels of diverse viral strains has been described. This method was evaluated using 19 Env-Abs, including CH103, against 181 diverse HIV-1 strains with available Ab-Ag complex structures. Chuang2013 (computational epitope prediction)
CH103: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. CH103-CH106 clonal variant antibodies were isolated from single memory B cells that were obtained using a fluorescently tagged Env as a bait. The unmutated common ancestor of the CH103 lineage bound the transmitted/founder Env glycoprotein, a trait critical for candidate immunogen to induce BnAbs. Co-crystal structure of CH103 revealed a new loop-based mechanism of CD4 binding site recognition and neutralization. The mature CH103 neutralized 55% of HIV isolates. Extensive viral diversification in and near CH103 epitope contributed to the evolution of neutralization breadth. Liao2013 (antibody generation, escape, structure, broad neutralizer)

References

Showing 35 of 35 references.

Isolation Paper
Liao2013 Hua-Xin Liao, Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, NISC Comparative Sequencing Program, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola, and Barton F. Haynes. Co-Evolution of a Broadly Neutralizing HIV-1 Antibody and Founder Virus. Nature, 496(7446):469-476, 25 Apr 2013. PubMed ID: 23552890. Show all entries for this paper.

Andrabi2018 Raiees Andrabi, Jinal N. Bhiman, and Dennis R. Burton. Strategies for a Multi-Stage Neutralizing Antibody-Based HIV Vaccine. Curr. Opin. Immunol., 53:143-151, 15 May 2018. PubMed ID: 29775847. Show all entries for this 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. Show all entries for this paper.

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. Show all entries for this paper.

Bradley2016a Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593. Show all entries for this paper.

Bricault2019 Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, and Bette Korber. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1):59-72.e8, 9 Jan 2019. PubMed ID: 30629920. Show all entries for this paper.

Burton2016 Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247. Show all entries for this paper.

Chuang2013 Gwo-Yu Chuang, Priyamvada Acharya, Stephen D. Schmidt, Yongping Yang, Mark K. Louder, Tongqing Zhou, Young Do Kwon, Marie Pancera, Robert T. Bailer, Nicole A. Doria-Rose, Michel C. Nussenzweig, John R. Mascola, Peter D. Kwong, and Ivelin S. Georgiev. Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains. J. Virol., 87(18):10047-10058, Sep 2013. PubMed ID: 23843642. Show all entries for this paper.

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. Show all entries for this paper.

Crooks2015 Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780. Show all entries for this paper.

Derking2015 Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248. Show all entries for this paper.

deTaeye2015 Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358. Show all entries for this paper.

Fera2014 Daniela Fera, Aaron G. Schmidt, Barton F. Haynes, Feng Gao, Hua-Xin Liao, Thomas B. Kepler, and Stephen C. Harrison. Affinity Maturation in an HIV Broadly Neutralizing B-Cell Lineage through Reorientation of Variable Domains. Proc. Natl. Acad. Sci. U.S.A., 111(28):10275-10280, 15 Jul 2014. PubMed ID: 24982157. Show all entries for this paper.

Freund2015 Natalia T. Freund, Joshua A. Horwitz, Lilian Nogueira, Stuart A. Sievers, Louise Scharf, Johannes F. Scheid, Anna Gazumyan, Cassie Liu, Klara Velinzon, Ariel Goldenthal, Rogier W. Sanders, John P. Moore, Pamela J. Bjorkman, Michael S. Seaman, Bruce D. Walker, Florian Klein, and Michel C. Nussenzweig. A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo. PLoS Pathog, 11(10):e1005238, Oct 2015. PubMed ID: 26516768. Show all entries for this paper.

Gao2014 Feng Gao, Mattia Bonsignori, Hua-Xin Liao, Amit Kumar, Shi-Mao Xia, Xiaozhi Lu, Fangping Cai, Kwan-Ki Hwang, Hongshuo Song, Tongqing Zhou, Rebecca M. Lynch, S. Munir Alam, M. Anthony Moody, Guido Ferrari, Mark Berrong, Garnett Kelsoe, George M. Shaw, Beatrice H. Hahn, David C. Montefiori, Gift Kamanga, Myron S. Cohen, Peter Hraber, Peter D. Kwong, Bette T. Korber, John R. Mascola, Thomas B. Kepler, and Barton F. Haynes. Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies. Cell, 158(3):481-491, 31 Jul 2014. PubMed ID: 25065977. Show all entries for this paper.

Georgiev2013a Ivelin S. Georgiev, M. Gordon Joyce, Tongqing Zhou, and Peter D. Kwong. Elicitation of HIV-1-Neutralizing Antibodies against the CD4-Binding Site. Curr. Opin. HIV AIDS, 8(5):382-392, Sep 2013. PubMed ID: 23924998. Show all entries for this paper.

Haynes2014 Barton F. Haynes, M.Anthony Moody, Munir Alam, Mattia Bonsignori, Laurent Verkoczy, Guido Ferrari, Feng Gao, Georgia D. Tomaras, Hua-Xin Liao, and Garnett Kelsoe. Progress in HIV-1 Vaccine Development. J. Allergy Clin. Immunol., 134(1):3-10, Jul 2014. PubMed ID: 25117798. Show all entries for this paper.

Henderson2019 Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, and S. Munir Alam. Selection of Immunoglobulin Elbow Region Mutations Impacts Interdomain Conformational Flexibility in HIV-1 Broadly Neutralizing Antibodies. Nat. Commun., 10(1):654, 8 Feb 2019. PubMed ID: 30737386. Show all entries for this paper.

Hraber2015 Peter Hraber, Bette Korber, Kshitij Wagh, Elena E. Giorgi, Tanmoy Bhattacharya, S. Gnanakaran, Alan S. Lapedes, Gerald H. Learn, Edward F. Kreider, Yingying Li, George M. Shaw, Beatrice H. Hahn, David C. Montefiori, S. Munir Alam, Mattia Bonsignori, M. Anthony Moody, Hua-Xin Liao, Feng Gao, and Barton F. Haynes. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants. Viruses, 7(10):5443-5475, 21 Oct 2015. PubMed ID: 26506369. Show all entries for this paper.

Korber2017 Bette Korber, Peter Hraber, Kshitij Wagh, and Beatrice H. Hahn. Polyvalent Vaccine Approaches to Combat HIV-1 Diversity. Immunol. Rev., 275(1):230-244, Jan 2017. PubMed ID: 28133800. Show all entries for this paper.

Kwong2013 Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Broadly Neutralizing Antibodies and the Search for an HIV-1 Vaccine: The End of the Beginning. Nat. Rev. Immunol., 13(9):693-701, Sep 2013. PubMed ID: 23969737. Show all entries for this paper.

LaBranche2018 Celia C. LaBranche, Andrew T. McGuire, Matthew D. Gray, Shay Behrens, Xuejun Chen, Tongqing Zhou, Quentin J. Sattentau, James Peacock, Amanda Eaton, Kelli Greene, Hongmei Gao, Haili Tang, Lautaro G. Perez, Kevin O. Saunders, Peter D. Kwong, John R. Mascola, Barton F. Haynes, Leonidas Stamatatos, and David C. Montefiori. HIV-1 Envelope Glycan Modifications That Permit Neutralization by Germline-Reverted VRC01-Class Broadly Neutralizing Antibodies. PLoS Pathog., 14(11):e1007431, Nov 2018. PubMed ID: 30395637. Show all entries for this paper.

Liu2015a Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869. Show all entries for this paper.

McHeyzer-Williams2014 Michael G. McHeyzer-Williams. B Cell Liaison Confounds HIV-1 Evolution. Cell, 158(3):475-476, 31 Jul 2014. PubMed ID: 25083862. Show all entries for this paper.

Moody2015 M. Anthony Moody, Feng Gao, Thaddeus C. Gurley, Joshua D. Amos, Amit Kumar, Bhavna Hora, Dawn J. Marshall, John F. Whitesides, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Kwan-Ki Hwang, Xiaozhi Lu, Mattia Bonsignori, Andrés Finzi, Nathan A. Vandergrift, S. Munir Alam, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, Gift Kamanga, Myron S. Cohen, Noel E. Sam, Saidi Kapiga, Elin S. Gray, Nancy L. Tumba, Lynn Morris, Susan Zolla-Pazner, Miroslaw K. Gorny, John R. Mascola, Beatrice H. Hahn, George M. Shaw, Joseph G. Sodroski, Hua-Xin Liao, David C. Montefiori, Peter T. Hraber, Bette T. Korber, and Barton F. Haynes. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host Microbe., 18(3):354-362, 9 Sep 2015. PubMed ID: 26355218. Show all entries for this paper.

Sanders2013 Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931. Show all entries for this paper.

Sanders2015 Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353. Show all entries for this paper.

Scheepers2015 Cathrine Scheepers, Ram K. Shrestha, Bronwen E. Lambson, Katherine J. L. Jackson, Imogen A. Wright, Dshanta Naicker, Mark Goosen, Leigh Berrie, Arshad Ismail, Nigel Garrett, Quarraisha Abdool Karim, Salim S. Abdool Karim, Penny L. Moore, Simon A. Travers, and Lynn Morris. Ability to Develop Broadly Neutralizing HIV-1 Antibodies Is Not Restricted by the Germline Ig Gene Repertoire. J. Immunol., 194(9):4371-4378, 1 May 2015. PubMed ID: 25825450. Show all entries for this paper.

Sheng2016 Zizhang Sheng, Chaim A. Schramm, Mark Connors, Lynn Morris, John R. Mascola, Peter D. Kwong, and Lawrence Shapiro. Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection. PLoS Comput. Biol., 12(5):e1004940, May 2016. PubMed ID: 27191167. Show all entries for this paper.

Sliepen2015 Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050. Show all entries for this paper.

Stewart-Jones2016 Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034. Show all entries for this paper.

Williams2017a Wilton B. Williams, Jinsong Zhang, Chuancang Jiang, Nathan I. Nicely, Daniela Fera, Kan Luo, M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Thomas B. Kepler, Akshaya Ramesh, Kevin Wiehe, James A. Holland, Todd Bradley, Nathan Vandergrift, Kevin O. Saunders, Robert Parks, Andrew Foulger, Shi-Mao Xia, Mattia Bonsignori, David C. Montefiori, Mark Louder, Amanda Eaton, Sampa Santra, Richard Scearce, Laura Sutherland, Amanda Newman, Hilary Bouton-Verville, Cindy Bowman, Howard Bomze, Feng Gao, Dawn J. Marshall, John F. Whitesides, Xiaoyan Nie, Garnett Kelsoe, Steven G. Reed, Christopher B. Fox, Kim Clary, Marguerite Koutsoukos, David Franco, John R. Mascola, Stephen C. Harrison, Barton F. Haynes, and Laurent Verkoczy. Initiation of HIV Neutralizing B Cell Lineages with Sequential Envelope Immunizations. Nat. Commun., 8(1):1732, 23 Nov 2017. PubMed ID: 29170366. Show all entries for this paper.

Wu2016 Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425. Show all entries for this paper.

Zhou2015 Tongqing Zhou, Rebecca M. Lynch, Lei Chen, Priyamvada Acharya, Xueling Wu, Nicole A. Doria-Rose, M. Gordon Joyce, Daniel Lingwood, Cinque Soto, Robert T. Bailer, Michael J. Ernandes, Rui Kong, Nancy S. Longo, Mark K. Louder, Krisha McKee, Sijy O'Dell, Stephen D. Schmidt, Lillian Tran, Zhongjia Yang, Aliaksandr Druz, Timothy S. Luongo, Stephanie Moquin, Sanjay Srivatsan, Yongping Yang, Baoshan Zhang, Anqi Zheng, Marie Pancera, Tatsiana Kirys, Ivelin S. Georgiev, Tatyana Gindin, Hung-Pin Peng, An-Suei Yang, NISC Comparative Sequencing Program, James C. Mullikin, Matthew D. Gray, Leonidas Stamatatos, Dennis R. Burton, Wayne C. Koff, Myron S. Cohen, Barton F. Haynes, Joseph P. Casazza, Mark Connors, Davide Corti, Antonio Lanzavecchia, Quentin J. Sattentau, Robin A. Weiss, Anthony P. West, Jr., Pamela J. Bjorkman, Johannes F. Scheid, Michel C. Nussenzweig, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell, 161(6):1280-1292, 4 Jun 2015. PubMed ID: 26004070. Show all entries for this paper.

Zhou2017 Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724. Show all entries for this paper.

Displaying record number 2862

Download this epitope record as JSON.

MAb ID	CH104
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Subtype	C
Ab Type	gp120 CD4BS
Neutralizing	P View neutralization details
Species (Isotype)	human(IgG1)
Patient	Donor CH505
Immunogen	HIV-1 infection
Keywords	antibody generation, antibody lineage, antibody sequence, binding affinity, broad neutralizer, escape, neutralization, review, structure

Notes

Showing 8 of 8 notes.

CH104: 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)
CH104: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's V_L and V_H 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 K_d increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower K_ds and K_as over maturation. CH104 neutralized 100% of an 113-patient CH505-derived autologous pseudoviral panel as part of CH103 lineages, at a potency of <50 µg/ml. Bonsignori2016 (neutralization, binding affinity, antibody sequence, antibody lineage)
CH104: A computational method, LASSIE (Longitudinal Antigenic Sequences and Sites from Intrahost Evolution), uses transmitted founder loss to identify virus hot-spots under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. Sequences and antibodies from patient CH505 were used to demonstrate the methodology. The neutralization of CH103, members of its clonal lineage (CH104, CH105, CH106), and its ancestral antibodies (IA1 - IA8 and UCA) were assayed against longitudinal Env sequences from patient CH505. Neutralization and binding assay results confirmed that selected viruses exhibited diverse antibody sensitivities, which increased with maturation of the bnAb lineage and generally followed the progression of mutations away from the TF virus. CH104 neutralized 97% of a panel of autologous env gp160s at IC₅₀ <50 µg/ml. Hraber2015 (neutralization, antibody lineage)
CH104: Structures of progenitor and intermediate antibodies to CH103 lineage were analyzed. The critical feature of affinity maturation in the CH103 lineage was shown to be a small but significant shift in the relative orientations of VH and VL domains. The mutations leading to the conformational shift probably occurred in response to insertions into V5 in gp120 of autologous viruses, illustrating a mechanism of affinity maturation through mutation outside the Ag combining site. CH104 has comparable affinities for gp120 with CH103, which has a three-residue deletion in CDRL1. Fera2014 (neutralization, escape, structure, antibody lineage)
CH104: Advances (newly discovered Env targeting antibodies, CTL-control of infection, correlates of transmission risk, co-evolution of Env with bNAb, immunogens that overcome CTL epitope diversity) and promising approaches for HIV-1 vaccines were reviewed. CH104 lineage co-evolution with HIV-1 Env was discussed. Haynes2014 (neutralization, review)
CH104: This comment points out that Gao2013 et al. have uncovered an intermediate stage in the process of bnAb production. Viral escape from one B cell lineage, CH235, seen as mutations in the CD4bs D-loop, is then followed by emergence of the bnAb CH103 and its members (CH104, CH105, CH106), that not only bind those D-loop variants but also demonstrate broad cross-reactivity and neutralization potency. McHeyzer-Williams2014 (review)
CH104: As compared to early mutations in V- and CD4-binding loops that result in escape from antibody CH103, mutations in patient CH505's HIV-1 Env loop D generated a virus variant that showed increased binding to and neutralizaton by bnAb CH103 as well as mature CH104. The Env loop D mutations were driven by an independent antibody from a separate B-lineage, CH235. Thus, co-operation between 2 different B cell lineages in early infection induced potent, cross-reactive bnAb CH103 development. Gao2014 (antibody generation, neutralization, binding affinity, broad neutralizer)
CH104: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. CH103-CH106 clonal variant antibodies were isolated from single memory B cells that were obtained using a fluorescently tagged Env as a bait. The unmutated common ancestor of the CH103 lineage bound the transmitted/founder Env glycoprotein, a trait critical for candidate immunogen to induce BnAbs. Liao2013 (antibody generation, escape)

References

Showing 8 of 8 references.

McHeyzer-Williams2014 Michael G. McHeyzer-Williams. B Cell Liaison Confounds HIV-1 Evolution. Cell, 158(3):475-476, 31 Jul 2014. PubMed ID: 25083862. Show all entries for this paper.

Displaying record number 2863

Download this epitope record as JSON.

MAb ID	CH105
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Subtype	C
Ab Type	gp120 CD4BS
Neutralizing	P View neutralization details
Species (Isotype)	human(IgG1)
Patient	Donor CH505
Immunogen	HIV-1 infection
Keywords	antibody generation, antibody lineage, antibody sequence, binding affinity, broad neutralizer, escape, neutralization, review, structure

Notes

Showing 8 of 8 notes.

CH105: 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)
CH105: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's V_L and V_H 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 K_d increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower K_ds and K_as over maturation. CH105 neutralized 100% of an 113-patient CH505-derived autologous pseudoviral panel as part of CH103 lineages, at a potency of <50 µg/ml. Bonsignori2016 (neutralization, binding affinity, antibody sequence, antibody lineage)
CH105: A computational method, LASSIE (Longitudinal Antigenic Sequences and Sites from Intrahost Evolution), uses transmitted founder loss to identify virus hot-spots under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. Sequences and antibodies from patient CH505 were used to demonstrate the methodology. The neutralization of CH103, members of its clonal lineage (CH104, CH105, CH106), and its ancestral antibodies (IA1 - IA8 and UCA) were assayed against longitudinal Env sequences from patient CH505. Neutralization and binding assay results confirmed that selected viruses exhibited diverse antibody sensitivities, which increased with maturation of the bnAb lineage and generally followed the progression of mutations away from the TF virus. CH105 neutralized 93% of a panel of autologous env gp160s at IC₅₀ <50 µg/ml. Hraber2015 (neutralization, antibody lineage)
CH105: Structures of progenitor and intermediate antibodies to CH103 lineage were analyzed. The critical feature of affinity maturation in the CH103 lineage was shown to be a small but significant shift in the relative orientations of VH and VL domains. The mutations leading to the conformational shift probably occurred in response to insertions into V5 in gp120 of autologous viruses, illustrating a mechanism of affinity maturation through mutation outside the Ag combining site. Fera2014 (neutralization, escape, structure, antibody lineage)
CH105: Advances (newly discovered Env targeting antibodies, CTL-control of infection, correlates of transmission risk, co-evolution of Env with bNAb, immunogens that overcome CTL epitope diversity) and promising approaches for HIV-1 vaccines were reviewed. CH105 lineage co-evolution with HIV-1 Env was discussed. Haynes2014 (neutralization, review)
CH105: This comment points out that Gao2013 et al. have uncovered an intermediate stage in the process of bnAb production. Viral escape from one B cell lineage, CH235, seen as mutations in the CD4bs D-loop, is then followed by emergence of the bnAb CH103 and its members (CH104, CH105, CH106), that not only bind those D-loop variants but also demonstrate broad cross-reactivity and neutralization potency. McHeyzer-Williams2014 (review)
CH105: As compared to early mutations in V- and CD4-binding loops that result in escape from antibody CH103, mutations in patient CH505's HIV-1 Env loop D generated a virus variant that showed increased binding to and neutralizaton by bnAb CH103, as well as mature CH105. The Env loop D mutations were driven by an independent antibody from a separate B-lineage, CH235. Thus, co-operation between 2 different B cell lineages in early infection induced potent, cross-reactive bnAb CH103 development. Gao2014 (antibody generation, neutralization, binding affinity, broad neutralizer)
CH105: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. CH103-CH106 clonal variant antibodies were isolated from single memory B cells that were obtained using a fluorescently tagged Env as a bait. The unmutated common ancestor of the CH103 lineage bound the transmitted/founder Env glycoprotein, a trait critical for candidate immunogen to induce BnAbs. Liao2013 (antibody generation, escape)

References

Showing 8 of 8 references.

McHeyzer-Williams2014 Michael G. McHeyzer-Williams. B Cell Liaison Confounds HIV-1 Evolution. Cell, 158(3):475-476, 31 Jul 2014. PubMed ID: 25083862. Show all entries for this paper.

Displaying record number 2864

Download this epitope record as JSON.

MAb ID	CH106
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Subtype	C
Ab Type	gp120 CD4BS
Neutralizing	P View neutralization details
Species (Isotype)	human(IgG1)
Patient	Donor CH505
Immunogen	HIV-1 infection
Keywords	antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, chimeric antibody, escape, glycosylation, neutralization, review, structure, vaccine antigen design, vaccine-induced immune responses

Notes

Showing 14 of 14 notes.

CH106: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q). Yates2018 (vaccine antigen design, vaccine-induced immune responses, binding affinity)
CH106: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. CH106 is polyreactive, but not autoreactive. Liu2015a (autoantibody or autoimmunity, antibody polyreactivity)
CH106: This study reports host tolerance mechanisms that limit the development of CD4bs and HCDR3-binder bNAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs bnAbs recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env + B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing. Stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development. DH522.1 and DH522.2 showed competition for binding epitopes targeted by CH106. Williams2017a (glycosylation, structure, antibody lineage, chimeric antibody)
CH106: 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)
CH106: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among CD4bs binding bNAbs, CH106 recognizes trimer similarly to 1NC9, CH103, 3BNC117 and VRC01, and is inhibited by sCD4. Derking2015 (antibody interactions, neutralization, binding affinity, structure)
CH106: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4bs bNAb CH106 neutralized BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and was shown to recognize and bind the immunogen too. Sanders2013 (assay or method development, neutralization, binding affinity)
CH106: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's V_L and V_H chains at 17 time points 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 K_d increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower K_ds and K_as over maturation. CH106 neutralized 100% of an 113-patient CH505-derived autologous pseudoviral panel as part of CH103 lineages, at a potency of <50 µg/ml. Except for CH241, earlier maturation intermediates of the CH235 lineage antibodies can not outcompete CH106, while CH106 effectively blocks binding of mature CH235 lineage bNAbs. Bonsignori2016 (neutralization, binding affinity, antibody sequence, antibody lineage)
CH106: A computational method, LASSIE (Longitudinal Antigenic Sequences and Sites from Intrahost Evolution), uses transmitted founder loss to identify virus hot-spots under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. Sequences and antibodies from patient CH505 were used to demonstrate the methodology. The neutralization of CH103, members of its clonal lineage (CH104, CH105, CH106), and its ancestral antibodies (IA1 - IA8 and UCA) were assayed against longitudinal Env sequences from patient CH505. Neutralization and binding assay results confirmed that selected viruses exhibited diverse antibody sensitivities, which increased with maturation of the bnAb lineage and generally followed the progression of mutations away from the TF virus. CH106 neutralized 98% of a panel of autologous env gp160s at IC₅₀ <50 µg/ml. Hraber2015 (neutralization, antibody lineage)
CH106: This study examined the development and co-evolution of autologous antibodies and viruses in two patients. Antibodies with limited heterologous breadth were able to potently neutralize autologous viruses, and such antibodies could select for neutralization-resistant autologous viruses implicated in transmission. Viruses from subject CH0457 were largely susceptible to neutralization by CD4bs-binding heterologous nAbs CH31 and CH106. Loop-binding CD4bs-bnAb CH106 was able to neutralize 89% of an autologous, 84-pseudoviral panel from CH0457. Moody2015 (neutralization)
CH106: Structures of progenitor and intermediate antibodies to CH103 lineage were analyzed. The critical feature of affinity maturation in the CH103 lineage was shown to be a small but significant shift in the relative orientations of VH and VL domains. The mutations leading to the conformational shift probably occurred in response to insertions into V5 in gp120 of autologous viruses, illustrating a mechanism of affinity maturation through mutation outside the Ag combining site. CH106 has comparable affinities for gp120 with CH103, which has a three-residue deletion in CDRL1. Fera2014 (neutralization, escape, structure, antibody lineage)
CH106: Advances (newly discovered Env targeting antibodies, CTL-control of infection, correlates of transmission risk, co-evolution of Env with bNAb, immunogens that overcome CTL epitope diversity) and promising approaches for HIV-1 vaccines were reviewed. CH106 lineage co-evolution with HIV-1 Env was discussed. Haynes2014 (neutralization, review)
CH106: This comment points out that Gao2013 et al. have uncovered an intermediate stage in the process of bnAb production. Viral escape from one B cell lineage, CH235, seen as mutations in the CD4bs D-loop, is then followed by emergence of the bnAb CH103 and its members (CH104, CH105, CH106), that not only bind those D-loop variants but also demonstrate broad cross-reactivity and neutralization potency. McHeyzer-Williams2014 (review)
CH106: As compared to early mutations in V- and CD4-binding loops that result in escape from antibody CH103, mutations in patient CH505's HIV-1 Env loop D generated a virus variant that showed increased binding to and neutralizaton by bnAb CH103, as well as mature CH106. The Env loop D mutations were driven by an independent antibody from a separate B-lineage, CH235. Thus, co-operation between 2 different B cell lineages in early infection induced potent, cross-reactive bnAb CH103 development. Gao2014 (antibody generation, neutralization, binding affinity, broad neutralizer)
CH106: Concomitant virus evolution and antibody maturation, leading to induction of a lineage of broadly neutralizing antibodies CH103-CH106, were followed in an African patient CH505 for 34 months from the time of infection. CH103-CH106 clonal variant antibodies were isolated from single memory B cells that were obtained using a fluorescently tagged Env as a bait. The unmutated common ancestor of the CH103 lineage bound the transmitted/founder Env glycoprotein, a trait critical for candidate immunogen to induce BnAbs. Liao2013 (antibody generation, escape)

References

Showing 14 of 14 references.

McHeyzer-Williams2014 Michael G. McHeyzer-Williams. B Cell Liaison Confounds HIV-1 Evolution. Cell, 158(3):475-476, 31 Jul 2014. PubMed ID: 25083862. Show all entries for this paper.

Yates2018 Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288. Show all entries for this paper.