5DT1

Crystal structure of human Fab CAP256-VRC26.25, a potent V1V2-directed HIV-1 broadly neutralizing antibody

Summary for 5DT1

• Entry DOI: 10.2210/pdb5dt1/pdb
• Related: 4OCR 4OCS 4OCW 4OD1 4OD3 4ODH 4ORG
• Descriptor: Fab Heavy chain of broadly neutralizing antibody VRC26.25, Fab Light chain of broadly neutralizing antibody VRC26.25, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: vrc26, cap256, v1v2, hiv-1, env, envelope, broadly neutralizing, superinfection, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 51722.64

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2015-09-17, release date: 2015-10-21, Last modification date: 2024-10-16)

Primary citation

Doria-Rose, N.A.,Bhiman, J.N.,Roark, R.S.,Schramm, C.A.,Gorman, J.,Chuang, G.Y.,Pancera, M.,Cale, E.M.,Ernandes, M.J.,Louder, M.K.,Asokan, M.,Bailer, R.T.,Druz, A.,Fraschilla, I.R.,Garrett, N.J.,Jarosinski, M.,Lynch, R.M.,McKee, K.,O'Dell, S.,Pegu, A.,Schmidt, S.D.,Staupe, R.P.,Sutton, M.S.,Wang, K.,Wibmer, C.K.,Haynes, B.F.,Abdool-Karim, S.,Shapiro, L.,Kwong, P.D.,Moore, P.L.,Morris, L.,Mascola, J.R.
New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency.
J.Virol., 90:76-91, 2015

PubMed Abstract: The epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development of these antibodies are providing insights for vaccination strategies. In addition, the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of 12 V1V2-directed neutralizing antibodies, CAP256-VRC26, isolated from an HIV-1 clade C-infected donor at years 1, 2, and 4 of infection (N. A. Doria-Rose et al., Nature 509:55-62, 2014, http://dx.doi.org/10.1038/nature13036). Here, we report on the isolation and characterization of new members of the family mostly obtained at time points of peak serum neutralization breadth and potency. Thirteen antibodies were isolated from B cell culture, and eight were isolated using trimeric envelope probes for differential single B cell sorting. One of the new antibodies displayed a 10-fold greater neutralization potency than previously published lineage members. This antibody, CAP256-VRC26.25, neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency. Among the viruses neutralized, the median 50% inhibitory concentration was 0.001 μg/ml. All 33 lineage members targeted a quaternary epitope focused on V2. While all known bNAbs targeting the V1V2 region interact with the N160 glycan, the CAP256-VRC26 antibodies showed an inverse correlation of neutralization potency with dependence on this glycan. Overall, our results highlight the ongoing evolution within a single antibody lineage and describe more potent and broadly neutralizing members with potential clinical utility, particularly in areas where clade C is prevalent.

PubMed: 26468542
DOI: 10.1128/JVI.01791-15

Experimental method

X-RAY DIFFRACTION (1.954 Å)