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MAb ID	DH270.6
HXB2 Location	Env	Env Epitope Map
Author Location	gp120
Epitope
Subtype	C
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG)
Patient	CH848
Immunogen	HIV-1 infection
Country	Malawi
Keywords	antibody binding site, antibody generation, antibody lineage, antibody sequence, autologous responses, binding affinity, broad neutralizer, computational epitope prediction, contact residues, neutralization, structure, vaccine antigen design

Notes

Showing 4 of 4 notes.

DH270.6: 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. DH270.6 was used for analyzing clade sensitivity. Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
DH270.6: Crystal structure of Ab DH20.6 with the artificial mimetic immunogen for Env trimer, Man₉-V3 shows that DH270.6-Man₉-V3 conforms to intact HIV-1-Env. Two low probability somatic mutations, G57R and the later R98T increase neutralization breadth during Ab affinity maturation of DH270.6. Fera2018 (antibody binding site, structure, antibody lineage, broad neutralizer, contact residues)
DH270.6: Man₉-V3, a synthetic minimal immunogen designed to reflect the HIV-1 native Env V3-glycan bNAb epitope, binds memory B cells and V3-glycan bNAbs as well as germline bNAbs. Man₉-V3 was used to isolate a bNAb from an HIV-1+ subject and also induce V3-glycan-targeting antibodies in rhesus macaques. Using the crystal structure of PGT128-gp120 Env OD (outer domain), Man₉-V3 glycopeptide was synthesized based on Clade B JRFL with deletion of residues 305-320, retention of P321 and stabilization of disulfide bridge C296-C331. Man₉-V3 is bound by DH270 lineage bNAb. Alam2017 (antibody binding site)
DH270.6: The study isolated 3 new V3-glycan antibody lineages (DH270, DH272, DH475) from donor CH848, who was followed for 5 years starting from the time of transmission. The DH272 and DH475 lineages had neutralization patterns that likely selected for observed viral escape variants, which, in turn, stimulated the DH270 lineage to potent neutralization breadth. DH270 antibodies were recovered from memory B cells at all three sampling times (weeks 205, 232, and 234 post-infection). Clonal expansion occurred at week 186, concurrent with the development of plasma neutralization breadth. Like some previously-characterized Abs (PGT124, PGT128, PGT135), the DH270 lineage mAbs bound to Env N332, and their neutralization was reduced or abrogated by mutation of this residue. Bonsignori2017 (antibody binding site, antibody generation, autologous responses, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)

References

Showing 4 of 4 references.

Isolation Paper
Bonsignori2017 Mattia Bonsignori, Edward F. Kreider, Daniela Fera, R. Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S. Munir Alam, Baptiste Aussedat, William E. Walkowicz, Kwan-Ki Hwang, Kevin O. Saunders, Ruijun Zhang, Morgan A. Gladden, Anthony Monroe, Amit Kumar, Shi-Mao Xia, Melissa Cooper, Mark K. Louder, Krisha McKee, Robert T. Bailer, Brendan W. Pier, Claudia A. Jette, Garnett Kelsoe, Wilton B. Williams, Lynn Morris, John Kappes, Kshitij Wagh, Gift Kamanga, Myron S. Cohen, Peter T. Hraber, David C. Montefiori, Ashley Trama, Hua-Xin Liao, Thomas B. Kepler, M. Anthony Moody, Feng Gao, Samuel J. Danishefsky, John R. Mascola, George M. Shaw, Beatrice H. Hahn, Stephen C. Harrison, Bette T. Korber, and Barton F. Haynes. Staged Induction of HIV-1 Glycan-Dependent Broadly Neutralizing Antibodies. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298420. Show all entries for this paper.

Alam2017 S. Munir Alam, Baptiste Aussedat, Yusuf Vohra, R. Ryan Meyerhoff, Evan M. Cale, William E. Walkowicz, Nathan A. Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M. Gordon Joyce, Marie Pancera, Aliaksandr Druz, Ivelin S. Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven G. Reed, Mark Louder, Robert T. Bailer, Lynn Morris, Salim S. Abdool-Karim, Myron Cohen, Hua-Xin Liao, David C. Montefiori, Peter K. Park, Alberto Fernández-Tejada, Kevin Wiehe, Sampa Santra, Thomas B. Kepler, Kevin O. Saunders, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Mattia Bonsignori, M. Anthony Moody, Samuel Danishefsky, and Barton F. Haynes. Mimicry of an HIV Broadly Neutralizing Antibody Epitope with a Synthetic Glycopeptide. Sci. Transl. Med., 9(381), 15 Mar 2017. PubMed ID: 28298421. 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.

Fera2018 Daniela Fera, Matthew S. Lee, Kevin Wiehe, R. Ryan Meyerhoff, Alessandro Piai, Mattia Bonsignori, Baptiste Aussedat, William E. Walkowicz, Therese Ton, Jeffrey O. Zhou, Samuel Danishefsky, Barton F. Haynes, and Stephen C. Harrison. HIV Envelope V3 Region Mimic Embodies Key Features of a Broadly Neutralizing Antibody Lineage Epitope. Nat. Commun., 9(1):1111, 16 Mar 2018. PubMed ID: 29549260. Show all entries for this paper.