Search Antibody Database

Found 3 matching records:

Displaying record number 3509

Download this epitope record as JSON.

Notes

Showing 11 of 11 notes.

• N6: 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. N6 was chosen to represent a distinct group within the CD4bs category, Class VRC01 as it was the broadest neutralizer. Chuang2019 (antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
• N6: A series of mutants was produced in the CAP256-VRC26.25 heavy chain, for the purpose of avoiding the previously-identified proteolytic cleavage at position K100m. Neutralization of the mutants was tested, and the cleavage-resistant variant that showed the greatest potency was K100mA. In addition to the K100mA mutation, an LS mutation was added to the Fc portion of the heavy chain, as this change has been shown to improve the half-life of antibodies used for passive administration without affecting neutralization potency. The resulting construct was named CAP256V2LS. The pharmacokinetics of CAP256V2LS were assessed in macaques and mice, and it showed a profile similar to other antibodies used for immunotherapy. The antibody lacked autoreactivity. Structural analysis of wild-type CAP256-VRC26.25 showed that the K100m residue is not involved in interaction with the Env trimer. Neutralization data for N6 and N6-LS were used for comparison purposes. Zhang2022 (neutralization, immunotherapy, broad neutralizer)
• N6: A novel CD4bs bNAb, 1-18, is identified with breadth (97% against a 119-strain multiclade panel) and potency exceeding (IC₅₀ = 0.048 µg/mL) most V_H1-46 and V_H1-2 class bNAbs like 3BNC117, VRC01, N6, 8ANC131, 10-1074, PGT151, PGT121, 8ANC195, PG16 and PGDM1400. 1-18 effectively restricts viral escape better than bNAbs 3BNC117 and VRC01. While 1-18 targets the CD4bs like VRC01-like Abs, it recognizes the epitope differently. Neutralizing activity against VRC01 Ab-class escapes is maintained by 1-18. In humanized mice infected by strain 1_YU2, viral suppression is also maintained by 1-18. V_H1-46-derived B cell clone 4.1 from patient IDC561 produced potent, broadly active Abs. Subclone 4.1 is characterized by a 6 aa CDRH1 insertion lengthening it from 8 to 14 aa. and produces bNAbs 1-18 and 1-55. Cryo-EM at 2.5A of 1-18 in complex with BG505_SOSIP.664 suggests their insertion increases inter-protomer contacts by a negatively charged DDDPYTDDD motif, resulting in an enlargement of the buried surface on HIV-1 gp120. Variations in glycosylation is thought to confer higher neutralizing activity on 1-18 over 1-55. Schommers2020 (antibody binding site, antibody generation, antibody interactions, neutralization, escape, binding affinity, antibody sequence, structure, broad neutralizer, contact residues)
• N6: The authors mutated two conserved tyrosine (Y) residues within the V2 loop of gp120 Y177 and Y173, individually or in combination, by replacing them with either phenylalanine (F) or alanine (A) in a clade B, tier 1B HIV-1 Env protein (BaL), and in a number of tier 2 HIV-1 Envs from different clades, namely, BG505 (clade A), JR-FL and JR-CSF (clade B), and CM244 (clade E). A consistent hierarchy of neutralization sensitivity was seen among the mutants, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The double-alanine mutation in mutant HIV-1 BaL, Y173A Y177A, increased sensitivity to all the weakly neutralizing MAbs tested and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site, such as F105, 654-30D, and b13. When tested against bNAbs instead, there was a trend to decrease neutralization sensitivity compared to WT, with the exception of N6, PGT151, 10E8, and 2G12, for which there was no change, and of 2F5 and 4E10, which were more effective against the mutant compared to the WT. Guzzo2018 (antibody binding site, binding affinity)
• N6: The authors engineered 10E8-surface mutants to improve its potency and screened for improved neutralization against a 9-virus panel. They created an optimized 10E8 antibody, called 10E8v4-5R+100cF, with mutations to phenylalanine and arginine, retained the extraordinary breadth of 10E8 but with ˜10-fold increased potency. N6, an anti-CD4BS bNAb, was one of the monoclonals used to test the new antibody in two-antibody combinations, and it yielded the best overall performance with 10E8v4-5R+100cF, neutralizing all strains in a 208-isolate HIV-1 panel at < 1µg/mL. Kwon2018 (neutralization)
• N6: 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. N6 was used for analyzing clade sensitivity. Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
• N6: In vitro neutralization data against 25 subtype A, 100 C, and 20 D pseudoviruses of 8 bNAbs (3BNC117, N6, VRC01, VRC07-523LS, CAP256-VRC26.25, PGDM1400, 10–1074, PGT121) and 2 bispecific Abs under clinical development (10E8-iMAb, 3BNC117-PGT135) was studied to assess the antibodies’ potential to prevent infection by dominant HIV-1 subtypes in sub-Saharan Africa. In vivo protection of these Abs and their 2-Ab combination was predicted using a function of in vitro neutralization based on data from a macaque simian-human immunodeficiency virus (SHIV) challenge study. Conclusions were that 1. bNAb combinations outperform individual bNAbs 2. Different bNAb combinations were optimal against different HIV subtypes 3. Bispecific 10E8-iMAb outperformed all combinations and 4. 10E8-iMAb in combination with other conventional Abs was predicted to be the best combination against HIV-infection. N6 was the best performing for subtypes A and C. N6 in combination with PGDM1400 was the best Ab combination against subtype A, while N6 + CAP256-VRC26.25 was best versus subtype D viruses. In the case of bispecific Ab combinations - for subtype A 10E8-iMAb with VRC07-523LS or N6 or PGDM1400 were best; 10E8-iMAb + N6 for subtype C which combination was also the best combination over all subtypes. Wagh2018 (immunotherapy)
• N6: This review summarizes current advances in antibody lineage-based design and epitope-based vaccine design. Antibody lineage-based design is described for VRC01, PGT121 and PG9 antibody classes, and epitope-based vaccine design is described for the CD4-binding site, as well as fusion peptide and glycan-V3 cites of vulnerability. Kwong2018 (antibody binding site, vaccine antigen design, vaccine-induced immune responses, review, antibody lineage, broad neutralizer, junction or fusion peptide)
• N6: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. N6 was isolated from human B cell clones and is functionally similar to VRC01. Antigenic region CD4 binding site (Table:1). Walker2018 (antibody binding site, review, broad neutralizer)
• N6: N6-LS, used in this study, is a variant of N6 containing two mutations (M428L and N434S) that result in an increased affinity for FcRn, thereby increasing plasma half-life. N6-LS, alone or in combination with the bnAb PGT121, was evaluated in rhesus macaques chronically infected with SHIV. N6-LS potently suppressed plasma viral loads in the majority of animals but the combination with PGT121 was not superior than PGT121 alone in delaying time to viral rebound or reducing PBMC or lymphnode cell proviral DNA levels. The occurrence of viral escape variants in an N6-LS mono-treated animal, however, suggests bNAb combination to maximize breadth would be beneficial for therapy. Julg2017 (immunotherapy)
• N6: Three novel antibodies (N6, F8, N17) were isolated from donor Z258, who was also the source of VRC27. N6 neutralized 98% of a panel of 181 pseudoviruses of diverse clades, including viruses resistant to VRC01 and VRC27. Epitope mapping revealed that N6 had a unique mode of recognition of the CD4 binding site.Its extraordinary breadth and potency were attributed to two mechanisms: (1) its binding was relatively insensitive to the loss of individual contacts and (2) it avoids the major mechanism of resistance to VRC01 class antibodies, specifically steric clashes resulting from changes in the vicinity of the V5 loop. The lineages of VRC27 and N6 evolved in parallel and may have had cooperative evolution, in which a helper lineage selects for HIV mutations that aid in the development of the other lineage. N6 did not exhibit autoreactivity or polyreactivity, making it a desirable candidate for clinical applications. Huang2016a (antibody generation, neutralization, antibody sequence, structure, antibody lineage, broad neutralizer)

References

Showing 11 of 11 references.

Isolation Paper
Huang2016a Jinghe Huang, Byong H. Kang, Elise Ishida, Tongqing Zhou, Trevor Griesman, Zizhang Sheng, Fan Wu, Nicole A. Doria-Rose, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Gwo-Yu Chuang, Aliaksandr Druz, Ivelin S. Georgiev, Chaim A. Schramm, Anqi Zheng, M. Gordon Joyce, Mangaiarkarasi Asokan, Amy Ransier, Sam Darko, Stephen A. Migueles, Robert T. Bailer, Mark K. Louder, S. Munir Alam, Robert Parks, Garnett Kelsoe, Tarra Von Holle, Barton F. Haynes, Daniel C. Douek, Vanessa Hirsch, Michael S. Seaman, Lawrence Shapiro, John R. Mascola, Peter D. Kwong, and Mark Connors. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. Immunity, 45(5):1108-1121, 15 Nov 2016. PubMed ID: 27851912. 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.

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.

Guzzo2018 Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178. Show all entries for this paper.

Julg2017 Boris Julg, Amarendra Pegu, Peter Abbink, Jinyan Liu, Amanda Brinkman, Katherine Molloy, Shanell Mojta, Abishek Chandrashekar, Katherine Callow, Keyun Wang, Xuejun Chen, Stephen D. Schmidt, Jinghe Huang, Richard A. Koup, Michael S. Seaman, Brandon F. Keele, John R. Mascola, Mark Connors, and Dan H. Barouch. Virological Control by the CD4-Binding Site Antibody N6 in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys. J. Virol., 91(16), 15 Aug 2017. PubMed ID: 28539448. Show all entries for this paper.

Kwon2018 Young D. Kwon, Gwo-Yu Chuang, Baoshan Zhang, Robert T. Bailer, Nicole A. Doria-Rose, Tatyana S. Gindin, Bob Lin, Mark K. Louder, Krisha McKee, Sijy O'Dell, Amarendra Pegu, Stephen D. Schmidt, Mangaiarkarasi Asokan, Xuejun Chen, Misook Choe, Ivelin S. Georgiev, Vivian Jin, Marie Pancera, Reda Rawi, Keyun Wang, Rajoshi Chaudhuri, Lisa A. Kueltzo, Slobodanka D. Manceva, John-Paul Todd, Diana G. Scorpio, Mikyung Kim, Ellis L. Reinherz, Kshitij Wagh, Bette M. Korber, Mark Connors, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody. Cell Rep., 22(7):1798-1809, 13 Feb 2018. PubMed ID: 29444432. Show all entries for this paper.

Kwong2018 Peter D. Kwong and John R. Mascola. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity, 48(5):855-871, 15 May 2018. PubMed ID: 29768174. Show all entries for this paper.

Schommers2020 Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Fätkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, and Florian Klein. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180(3):471-489.e22, 6 Feb 2020. PubMed ID: 32004464. Show all entries for this paper.

Wagh2018 Kshitij Wagh, Michael S. Seaman, Marshall Zingg, Tomas Fitzsimons, Dan H. Barouch, Dennis R. Burton, Mark Connors, David D. Ho, John R. Mascola, Michel C. Nussenzweig, Jeffrey Ravetch, Rajeev Gautam, Malcolm A. Martin, David C. Montefiori, and Bette Korber. Potential of Conventional \& Bispecific Broadly Neutralizing Antibodies for Prevention of HIV-1 Subtype A, C \& D Infections. PLoS Pathog., 14(3):e1006860, Mar 2018. PubMed ID: 29505593. Show all entries for this paper.

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. Show all entries for this paper.

Zhang2022 Baoshan Zhang, Jason Gorman, Sijy O’Dell, Leland F. Damron, Krisha McKee, Mangaiarkarasi Asokan, Amarendra Pegu, Bob C. Lin, Cara W. Chao, Xuejun Chen, Lucio Gama, Vera B. Ivleva, William H. Law, Cuiping Liu, Mark K. Louder, Stephen D. Schmidt, Chen-Hsiang Shen, Wei Shi, Judith A. Stein, Michael S. Seaman, Adrian B. McDermott, Kevin Carlton, John R. Mascola, Peter D. Kwong, Q. Paula Lei, and Nicole A. Doria-Rose. Engineering of {HIV-1} Neutralizing Antibody {CAP256V2LS} for Manufacturability and Improved Half Life, , :, 22 Apr 2022. Show all entries for this paper.

Displaying record number 3510

Download this epitope record as JSON.

Notes

Showing 1 of 1 note.

• N6: Three novel antibodies (N6, F8, N17) were isolated from donor Z258, who was also the source of VRC27. N6 neutralized 98% of a panel of 181 pseudoviruses of diverse clades, including viruses resistant to VRC01 and VRC27. F8 had somewhat lower breadth and potency. Huang2016a (antibody generation, neutralization, antibody sequence)

References

Showing 1 of 1 reference.

Isolation Paper
Huang2016a Jinghe Huang, Byong H. Kang, Elise Ishida, Tongqing Zhou, Trevor Griesman, Zizhang Sheng, Fan Wu, Nicole A. Doria-Rose, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Gwo-Yu Chuang, Aliaksandr Druz, Ivelin S. Georgiev, Chaim A. Schramm, Anqi Zheng, M. Gordon Joyce, Mangaiarkarasi Asokan, Amy Ransier, Sam Darko, Stephen A. Migueles, Robert T. Bailer, Mark K. Louder, S. Munir Alam, Robert Parks, Garnett Kelsoe, Tarra Von Holle, Barton F. Haynes, Daniel C. Douek, Vanessa Hirsch, Michael S. Seaman, Lawrence Shapiro, John R. Mascola, Peter D. Kwong, and Mark Connors. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. Immunity, 45(5):1108-1121, 15 Nov 2016. PubMed ID: 27851912. Show all entries for this paper.

Displaying record number 3511

Download this epitope record as JSON.

Notes

Showing 1 of 1 note.

• N17: Three novel antibodies (N6, F8, N17) were isolated from donor Z258, who was also the source of VRC27. N6 neutralized 98% of a panel of 181 pseudoviruses of diverse clades, including viruses resistant to VRC01 and VRC27. N17 had somewhat lower breadth and potency. Huang2016a (antibody generation, neutralization, antibody sequence)

References

Showing 1 of 1 reference.

Isolation Paper
Huang2016a Jinghe Huang, Byong H. Kang, Elise Ishida, Tongqing Zhou, Trevor Griesman, Zizhang Sheng, Fan Wu, Nicole A. Doria-Rose, Baoshan Zhang, Krisha McKee, Sijy O'Dell, Gwo-Yu Chuang, Aliaksandr Druz, Ivelin S. Georgiev, Chaim A. Schramm, Anqi Zheng, M. Gordon Joyce, Mangaiarkarasi Asokan, Amy Ransier, Sam Darko, Stephen A. Migueles, Robert T. Bailer, Mark K. Louder, S. Munir Alam, Robert Parks, Garnett Kelsoe, Tarra Von Holle, Barton F. Haynes, Daniel C. Douek, Vanessa Hirsch, Michael S. Seaman, Lawrence Shapiro, John R. Mascola, Peter D. Kwong, and Mark Connors. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. Immunity, 45(5):1108-1121, 15 Nov 2016. PubMed ID: 27851912. Show all entries for this paper.