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Displaying record number 3623
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MAb ID |
BG18 (354BG18) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp160 |
Epitope |
|
Subtype |
B |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
EB354 |
Immunogen |
HIV-1 infection |
Keywords |
anti-idiotype, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, binding affinity, broad neutralizer, germline, immunotherapy, neutralization, polyclonal antibodies, review, structure, therapeutic vaccine, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 13 of
13 notes.
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BG18: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. Only unglycosylated TGE320-328 (TGEIIGDIR) overlapped with the binding footprint of V3 glycan-targeting bnAb BG18.
Sengupta2023
(antibody binding site)
-
BG18: This article reviews how B cell receptor sequence analyses and repertoires can be used in vaccine stratagem. Overall, multiple immunogens and their interactions driving bnAb development to generate Abs with special genetic characteristics of V gene restriction, long CDRH3 and high load SHM are the current effective strategy being used. The contribution of immunogens eliciting BG18-like, long-CDRH3-containing bnAbs was recently seen to increase the normally exceedingly rare 0.01% of long-CDRH3 of sequences in healthy donors.
Kreer2020
(antibody generation, neutralization, therapeutic vaccine, review, antibody sequence)
-
BG18:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. BG18 was used as a reference control IgG. Inhibition of EPTC112 binding to SOSIP was mainly evidenced with anti-V3-glycan bNAb BG18/BG8 (55%–77% blocking range).
Molinos-Albert2023
(antibody binding site, binding affinity)
-
BG18: Using bnAb BG18 as a test case, this study validates a method to identify diverse pools of bnAb potential precursors that can be used as design targets to engineer HIV Env trimer priming immunogens. In a mouse model, a single priming immunization with ferritin nanoparticles displaying N332-GT2 Env trimers activated rare adoptively-transferred B cells expressing BG18 germline-reverted heavy chains and elicited antibody responses that could bind to diverse Env trimers with native-like modifications. The most promising vaccine candidates, BG505 SOSIP-based N332-GT1, N332-GT2, and N332-GT5, were used to isolate human BG18-like precursors which were then categorized into 2 types: Type I were characterized by having the same HCDR3 length, D gene, D gene reading frame, D gene position within HCDR3 and JH gene as BG18 (which were also the same criteria originally used to identify BG18-like precursors for design targets), while type II had VL3-25, VL3-1, or VL3-10 light chains paired with diverse heavy chains and HCDR3s with at least 20 aa. Type I and type II occurred at respective frequencies of ˜ 1 in 53 million and 7 million naive B cells. A 4.4-Å resolution cyro-EM structure of mature BG18 Fab bound to BG505 SOSIP.MD39 Env trimer was generated (PDB 6DFG). This demonstrated a similar HCDR3-dependent V1-straddling binding mode as germline-reverted BG18 (BG18 iGL) and isolated BG18-like precursors HMP1 (type I) and HMP42 (type II) Fabs, each complexed with N332-GT2 or N332-GT5 trimers.
Steichen2019
(vaccine antigen design, vaccine-induced immune responses, structure, antibody lineage, germline)
-
BG18: A macaque sequential immunization protocol with increasingly native-like V3-glycan-targeting Env trimers multimerized onto virus-like particles elicited multiple on-target mAbs with heterologous, yet generally weak, neutralization activity and minimal protection in a subsequent intrarectal heterologous challenge with SHIVDH12-V3AD8. The priming immunogen was RC1-4fill (clade A/E, RC1 with 4 additional glycans), a low affinity Env trimer with additional glycans to facilitate V3-glycan targeting and mask BG505 glycan hole, while the boosting immunogens were 11MUTB-4fill (clade A/E), B41-5MUT or B41 wildtype (clade B), AMC011/Du422 (clade B/C), and consensus group M/consensus clade C Env trimers. Rabbits were also immunized once with RC1-4 fill-VLP and produced V3-targeting mAbs with binding poses distinct from the known V3-targeting bnAbs (10-1074, PGT135, PGT128 and BG18).
Escolano2021
(vaccine antigen design, vaccine-induced immune responses)
-
BG18: 3 clonally-related autologously-neutralizing mAbs (43A, 43A1, and 43A2), isolated from rabbit 5743 which was co-immunized with BG505- and B41-based SOSIP soluble trimers [Klasse2016, PMID: 27627672], bind to an immunodominant epitope in V1 overlapping the bnAb N332 glycan supersite without interacting with glycans. BG18 made more extensive contacts with Env using its approx. 20 aa-long CDRH3, when compared to 43A2 which interacted with Env with its 13 aa CDRL3. Analysis of known crystal structure of mAbs BG18 and 35O22 bound to natively-glycosylated BG505 SOSIP.664 (PDB 6CH7) revealed that, compared to an unbound state, the V1 loop has undergone a conformational change that may provide more access to the GDIR motif.
Nogal2020
(antibody interactions, structure)
-
BG18: 14/17 cloned mAbs from mice, immunized with either modified native-like soluble Env trimer immunogen RC1 or RC1-4fill, and 32/38 cloned mAbs from macaques, immunized once with RC1-4fill multimerized on virus-like particles bound to the desired V3-glycan patch with diverse binding mechanisms. Germline usage and CDR sequence and length were identified for all 55 mAbs but only those with published functional characterization were included in this database. In macaques, these non-neutralizing mAbs had sequence and structural similarities to inferred germline precursors of bnAbs that target V3-glycan patch including longer light chain CDRs, CDRL3 QXXDSS & SYAG motifs, and CDRL1 NIG-like motifs. Compared to parental immunogen 11MUTB, both RC1 and RC1-4fill have N156 glycan deletion to facilitate V3-glycan patch binding while RC1-4fill also has glycans added at N230, N241, N289 and N344 to mask BG505-specific glycan hole. MAb BG18 efficiently bound RC1, RC1-4fill and BG505. The inferred germline (iGL) revertant for BG18 was not recognized by an anti-idiotypic Ab specific for the shared PGT121/10-1074 iGL revertant.
Escolano2019
(anti-idiotype)
-
BG18: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
BG18: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
BG18: IgA and IgG bNAbs of 3 distinct B cell lineages were characterized in a viremic controller (pt7). Two lineages comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. BNAb 7-269 in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation. Immunotherapy with 7-269 in humanized mice delayed viral rebound. AD8-infected cell killing by primary human natural killer (NK) cells via ADCC was observed with all pt7 bNAbs binding strongly to target cells and expressed as IgGs, except for 7-155. BNAbs in all three lineages targeted the N332 glycan supersite. Epitope mapping showed that all pt7 IgA and IgG bNAbs target the high-mannose patch centered on the N332 glycan without interacting with the V3 loop base, which contrasts with numerous bNAbs targeting the N332 supersite. The cryo-EM structure of 7-269 in complex with BG505 SOSIP revealed an epitope mainly composed of sugar residues comprising the N332 and N295 glycans; onto which 7-269 positions itself in a structurally similar way to 2G12. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers. Other antibodies used as controls included 10-188, 3BNC117, PGT121, PGT135, 10-1074, BG8, BG18, and SF12.
Lorin2022
(antibody binding site, binding affinity, structure)
-
BG18:This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. BG18 was isolated from human B cell clones and is functionally similar to super-Abs PGT121, PGT128 and PGT135. Antigenic region V3 glycan (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
BG18: A 3.8 Å crystal structure of the anti-V3 glycan bnAb, BG18, complexed with natively glycosylated Env Clade A trimer (BG505) or Clade B trimer (B41) shows that while BG18 D-gene encoded residues contact with HIV-1 N332gp120 and the gp120 GDIR peptide motif in a manner conserved with other V3/N332gp120 bnAbs PGT121 and 10-1074; it has a distinct orientation. This novel orientation provides additional contacts with N392gp120 and N386gp120 oligomannose glycans at the base of V3- and also contacts residues of the V1-loops and is due to rearrangements in the VH and VL domains. The increased surface contact with Env could account for the high potency of BG18. VH1-2 CD4bs-binding IOMA Ab (and gp120-gp41 interface-spanning Ab 35O22) binding modes to the Env trimer were not altered by binding of 3 BG18 Fabs in crystal structures of BG18-BG505-35O22, BG18-41-35O22 or BG18-BG505-IOMA.
Barnes2018
(therapeutic vaccine, structure)
-
BG18: Neutralizing antibodies were derived from long-term non-progressing donor EB354. Samples were donated at five different time points, enabling the isolation of three bNAbs (BG1, BG18, NC37) that largely account for the donor's serologic neutralizing activity. Sequencing of viruses from the donor revealed that viruses sensitive to the antibodies coexisted with the bNAbs for long periods of time. BG18, the most potent of the three antibodies, is directed against the Asn332 gp120-centered glycan patch at the base of the V3 loop. BG18 neutralized 64% of viruses in a 118-virus panel. BG18 utilizes germline genes IGHV4-4 and IGLV3-25. In a mouse model, monotherapy with BG18 transiently suppressed viremia, and the combination of BG18, NC37, and BG1 produced a prolonged and sustained drop in viremia.
Freund2017
(antibody generation, neutralization, immunotherapy, structure)
References
Showing 13 of
13 references.
Isolation Paper
Freund2017
Natalia T. Freund, Haoqing Wang, Louise Scharf, Lilian Nogueira, Joshua A. Horwitz, Yotam Bar-On, Jovana Golijanin, Stuart A. Sievers, Devin Sok, Hui Cai, Julio C. Cesar Lorenzi, Ariel Halper-Stromberg, Ildiko Toth, Alicja Piechocka-Trocha, Harry B. Gristick, Marit J. van Gils, Rogier W. Sanders, Lai-Xi Wang, Michael S. Seaman, Dennis R. Burton, Anna Gazumyan, Bruce D. Walker, Anthony P. West, Jr., Pamela J. Bjorkman, and Michel C. Nussenzweig. Coexistence of Potent HIV-1 Broadly Neutralizing Antibodies and Antibody-Sensitive Viruses in a Viremic Controller. Sci. Transl. Med., 9(373), 18 Jan 2017. PubMed ID: 28100831.
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Barnes2018
Christopher O. Barnes, Harry B. Gristick, Natalia T. Freund, Amelia Escolano, Artem Y. Lyubimov, Harald Hartweger, Anthony P. West, Jr., Aina E. Cohen, Michel C. Nussenzweig, and Pamela J. Bjorkman. Structural Characterization of a Highly-Potent V3-Glycan Broadly Neutralizing Antibody Bound to Natively-Glycosylated HIV-1 Envelope. Nat. Commun., 9(1):1251, 28 Mar 2018. PubMed ID: 29593217.
Show all entries for this paper.
Escolano2019
Amelia Escolano, Harry B. Gristick, Morgan E. Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y. Oliveira, Joy Pai, Anthony P. West, Jr., Christopher O. Barnes, Alexander A. Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R. Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V. Voll, David C. Montefiori, Michael S. Seaman, Anna Gazumyan, Murillo Silva, Andrew T. McGuire, Leonidas Stamatatos, Darrell J. Irvine, Lance Wells, Malcolm A. Martin, Pamela J. Bjorkman, and Michel C. Nussenzweig. Immunization Expands B Cells Specific to HIV-1 V3 Glycan in Mice and Macaques. Nature, 570(7762):468-473, Jun 2019. PubMed ID: 31142836.
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Escolano2021
Amelia Escolano, Harry .B Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A. G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jr., Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, and Pamela J. Bjorkman. Sequential Immunization of Macaques Elicits Heterologous Neutralizing Antibodies Targeting the V3-Glycan Patch of HIV-1 Env. Sci. Transl. Med., 13(621):eabk1533, 24 Nov 2021. PubMed ID: 34818054.
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Kreer2020
Christoph Kreer, Henning Gruell, Thierry Mora, Aleksandra M. Walczak, and Florian Klein. Exploiting B Cell Receptor Analyses to Inform on HIV-1 Vaccination Strategies. Vaccines (Basel), 8(1):13 doi, Jan 2020. PubMed ID: 31906351
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Lorin2022
Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gérard Péhau-Arnaudet, Dominik Hrebik, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, François Bontems, James P. Di Santo, Félix A. Rey, and Hugo Mouquet. Epitope Convergence of Broadly HIV-1 Neutralizing IgA and IgG Antibody Lineages in a Viremic Controller. J. Exp. Med., 219(3), 7 Mar 2022. PubMed ID: 35230385.
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Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
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Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
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Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
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Nogal2020
Bartek Nogal, Laura E. McCoy, Marit J. van Gils, Christopher A. Cottrell, James E. Voss, Raiees Andrabi, Matthias Pauthner, Chi-Hui Liang, Terrence Messmer, Rebecca Nedellec, Mia Shin, Hannah L. Turner, Gabriel Ozorowski, Rogier W. Sanders, Dennis R. Burton, and Andrew B. Ward. HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite. Sci. Adv., 6(23):eaba0512, Jun 2020. PubMed ID: 32548265.
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Steichen2019
Jon M. Steichen, Ying-Cing Lin, Colin Havenar-Daughton, Simone Pecetta, Gabriel Ozorowski, Jordan R. Willis, Laura Toy, Devin Sok, Alessia Liguori, Sven Kratochvil, Jonathan L. Torres, Oleksandr Kalyuzhniy, Eleonora Melzi, Daniel W. Kulp, Sebastian Raemisch, Xiaozhen Hu, Steffen M. Bernard, Erik Georgeson, Nicole Phelps, Yumiko Adachi, Michael Kubitz, Elise Landais, Jeffrey Umotoy, Amanda Robinson, Bryan Briney, Ian A. Wilson, Dennis R. Burton, Andrew B. Ward, Shane Crotty, Facundo D. Batista, and William R. Schief. A Generalized HIV Vaccine Design Strategy for Priming of Broadly Neutralizing Antibody Responses. Science, 366(6470), 6 Dec 2019. PubMed ID: 31672916.
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Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
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Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
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