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- EMDB-49511: CH35 V1V2V3 and gp41-base macaque polyclonal Fabs in complex with... -

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Basic information

Entry
Database: EMDB / ID: EMD-49511
TitleCH35 V1V2V3 and gp41-base macaque polyclonal Fabs in complex with Q23-APEX-GT2 trimer
Map datamain map
Sample
  • Complex: CH35 V1V2V3 and gp41-base macaque polyclonal Fabs in complex with Q23-APEX-GT2 trimer
KeywordsEMPEM / NHP / Apex / germline targeting / polyclonal / HIV / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Biological speciesMacaca mulatta (Rhesus monkey)
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
AuthorsLee W-H / Ozorowski G / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)UM1AI144462 United States
CitationJournal: Immunity / Year: 2026
Title: Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.
Authors: Nitesh Mishra / Bo Liang / Ryan S Roark / Amrit Raj Ghosh / Sean Callaghan / Wen-Hsin Lee / Xuduo Li / Anh L Vo / Gabriel Avillion / Rohan Roy Chowdhury / Rumi Habib / Frederic Bibollet- ...Authors: Nitesh Mishra / Bo Liang / Ryan S Roark / Amrit Raj Ghosh / Sean Callaghan / Wen-Hsin Lee / Xuduo Li / Anh L Vo / Gabriel Avillion / Rohan Roy Chowdhury / Rumi Habib / Frederic Bibollet-Ruche / Gabriella Giese / Prabhgun Oberoi / Khaled Amereh / Anjali Somanathan / Yuxin Zhu / Yuexiu Zhang / Muzaffer Kassab / Lifei Tjio / Sharaf Andrabi / Raphael A Reyes / Joel D Allen / Nicole E James / Kipchoge N Randall / Lara van der Maas / Elana Ben-Akiva / Kasia Kacmarek-Michaels / Samantha Plante / Christian L Martella / Ashwin N Skelly / Ajay Singh / Jonathan Hurtado / Katharina Dueker / Tazio Capozzola / Rebecca Nedellec / Gabriel Ozorowski / Mark G Lewis / Samantha Falcone / Andrea Carfi / Sunny Himansu / Lawrence Shapiro / Max Crispin / Beatrice H Hahn / Bryan Briney / Darrell J Irvine / Dennis R Burton / Andrew B Ward / Facundo D Batista / Peter D Kwong / George M Shaw / Raiees Andrabi /
Abstract: Germline targeting (GT) is a promising strategy to activate rare broadly neutralizing antibody (bnAb)-producing B cells against HIV, but induction of such responses in outbred animals has not been ...Germline targeting (GT) is a promising strategy to activate rare broadly neutralizing antibody (bnAb)-producing B cells against HIV, but induction of such responses in outbred animals has not been achieved. Using antibody-guided structure-based design, we engineered a GT HIV trimer immunogen, Q23-APEX-GT2, which primes diverse V2-apex bnAb precursors. Q23-APEX-GT2 efficiently activated rare V2-apex-specific B cells in humanized knockin mice and consistently elicited immunofocused antibody responses in outbred rhesus macaques, priming multiple long heavy-chain complementarity-determining region 3 (CDRH3)-loop bnAb-B cell lineages. Monoclonal antibodies isolated from immunized macaques showed broad heterologous HIV trimer recognition and modest cross-neutralization of diverse tier-2 viruses. Cryoelectron microscopy (cryo-EM) structural studies confirmed precise epitope targeting and revealed CDRH3-mediated binding modes that mirrored those of human V2-apex bnAbs. Together, these findings establish proof of principle for priming and early maturation of authentic V2-apex bnAb precursors in outbred macaques and highlight the promise of V2-apex-targeted HIV vaccines.
History
DepositionFeb 28, 2025-
Header (metadata) releaseApr 1, 2026-
Map releaseApr 1, 2026-
UpdateApr 29, 2026-
Current statusApr 29, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_49511.png

Downloads & links

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Map

FileDownload / File: emd_49511.map.gz / Format: CCP4 / Size: 3.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmain map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
3.78 Å/pix.
x 96 pix.
= 362.88 Å		3.78 Å/pix.
x 96 pix.
= 362.88 Å		3.78 Å/pix.
x 96 pix.
= 362.88 Å

Surface

Projections

Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 3.78 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.01
Minimum - Maximum-0.039415084 - 0.057619445
Average (Standard dev.)0.00009344543 (±0.003317181)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions969696
Spacing969696
CellA=B=C: 362.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half map A

Fileemd_49511_half_map_1.map
Annotationhalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_49511_half_map_2.map
Annotationhalf map B
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : CH35 V1V2V3 and gp41-base macaque polyclonal Fabs in complex with...

EntireName: CH35 V1V2V3 and gp41-base macaque polyclonal Fabs in complex with Q23-APEX-GT2 trimer
Components
  • Complex: CH35 V1V2V3 and gp41-base macaque polyclonal Fabs in complex with Q23-APEX-GT2 trimer

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Supramolecule #1: CH35 V1V2V3 and gp41-base macaque polyclonal Fabs in complex with...

SupramoleculeName: CH35 V1V2V3 and gp41-base macaque polyclonal Fabs in complex with Q23-APEX-GT2 trimer
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Macaca mulatta (Rhesus monkey)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.03 mg/mL
BufferpH: 7.4
StainingType: NEGATIVE / Material: uranyl formate
GridModel: Homemade / Material: COPPER / Mesh: 400 / Support film - Material: CARBON

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm

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Image processing

CTF correctionType: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6v0r


Details: coordinates converted to map and low pass filtered to 40 Angstrom
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 25.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 4.0b1) / Number images used: 30098
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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