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MAb ID	10-1074V
HXB2 Location	Env	Env Epitope Map
Author Location	Env
Epitope
Subtype	A
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P (tier 2) View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human
Patient	Donor 17
Immunogen	HIV-1 infection
Keywords	antibody binding site, assay or method development, broad neutralizer, computational epitope prediction, immunotherapy, neutralization, vaccine antigen design

Notes

Showing 4 of 4 notes.

10-1074V: 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. 10-1074V was used for analyzing clade sensitivity. Bricault2019 (antibody binding site, vaccine antigen design, computational epitope prediction, broad neutralizer)
10-1074V: Panels of C clade pseudoviruses were computationally downselected from the panel of 200 C clade viruses defined by Rademeyer et al. 2016. A 12-virus panel was defined for the purpose of screening sera from vaccinees. Panels of 50 and 100 viruses were defined as smaller sets for use in testing magnitude and breadth against C clade. Published neutralization data for 16 mAbs was taken from CATNAP for the computational selections: 10-1074, 10-1074V, PGT121, PGT128, VRC26.25, VRC26.08, PGDM1400, PG9, PGT145, VRC07-523, 10E8, VRC13, 3BNC117, VRC07, VRC01, 4E10. Hraber2017 (assay or method development, neutralization)
10-1074V: Database note: 10-1074V is a variant of mAb 10–1074 in which six complex-type glycan-contacting residues in IgH have been substituted with those from mAb PGT121. As of 5/2018, a detailed description of the derivation of this bNAb has not been published.
10-1074V: Double, triple or quadruple combinations of fifteen bNAbs that target 4 distinct epitope regions: the CD4 binding site (3BNC117, VRC01, VRC07, VRC07-523, VRC13), the V3-glycan supersite (10–1074, 10-1074V, PGT121, PGT128), the V1/V2-glycan site (PG9, PGT145, PGDM1400, CAP256-VRC26.08, CAP256-VRC26.25), and the gp41 MPER epitope (10E8) were studied. Their neutralization potency and breadth were assayed against a panel of 200 acute/early subtype C strains, and compared to a novel, highly accurate predictive mathematical model (no-overlap Bliss Hill model, CombiNaber tool, LANL HIV Immunology database). These data were used to predict the best combinations of bNAbs for immunotherapy. Wagh2016 (neutralization, immunotherapy)

References

Showing 3 of 3 references.

Wagh2016 Kshitij Wagh, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, Cecilia Rademeyer, Hyejin Yoon, Alan Lapedes, Hongmei Gao, Kelli Greene, Mark K. Louder, Rui Kong, Salim Abdool Karim, Dennis R. Burton, Dan H. Barouch, Michel C. Nussenzweig, John R. Mascola, Lynn Morris, David C. Montefiori, Bette Korber, and Michael S. Seaman. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog., 12(3):e1005520, Mar 2016. PubMed ID: 27028935. Show all entries for this paper.

Hraber2017 Peter Hraber, Cecilia Rademeyer, Carolyn Williamson, Michael S. Seaman, Raphael Gottardo, Haili Tang, Kelli Greene, Hongmei Gao, Celia LaBranche, John R. Mascola, Lynn Morris, David C. Montefiori, and Bette Korber. Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments. J. Virol., 91(19), 1 Oct 2017. PubMed ID: 28747500. 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.