Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

 PMID:30076101  

Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.

Hongying Duan | Xuejun Chen | Jeffrey C Boyington | Cheng Cheng | Yi Zhang | Alexander J Jafari | Tyler Stephens | Yaroslav Tsybovsky | Oleksandr Kalyuzhniy | Peng Zhao | Sergey Menis | Martha C Nason | Erica Normandin | Maryam Mukhamedova | Brandon J DeKosky | Lance Wells | William R Schief | Ming Tian | Frederick W Alt | Peter D Kwong | John R Mascola
Immunity | 2018

An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env). An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials. However, a substantial portion of eOD-GT8-elicited antibodies target non-CD4bs epitopes, potentially limiting its efficacy. We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment. Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors. These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.

Pubmed ID: 30076101

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


NetNGlyc (tool)

RRID:SCR_001570

Server that predicts N-Glycosylation sites in human proteins using artificial neural networks that examine the sequence context of Asn-Xaa-Ser/Thr sequons. NetNGlyc 1.0 is also available as a stand-alone software package, with the same functionality as the service above. Ready-to-ship packages exist for the most common UNIX platforms.

View all literature mentions

SerialEM (tool)

RRID:SCR_017293

Software tool for automated EM data acquisition. Used for efficient tilt series acquisition and interface for image capture, display, and storage and for control of some aspects of microscope function.

View all literature mentions

IgG1 (antibody)

RRID:AB_394862

This monoclonal targets IgG1

View all literature mentions

VRC03 antibody (antibody)

RRID:AB_2491021

This monoclonal targets HIV-1 Envelope CD4 binding site

View all literature mentions

Goat Anti-Human (H L) HRP conjugate (antibody)

RRID:AB_11125935

This unknown targets Goat Human (H L) HRP conjugate

View all literature mentions

Goat Anti-Mouse IgG (H L)-HRP Conjugate (antibody)

RRID:AB_11125547

This unknown targets Goat Mouse IgG (H L)-HRP Conjugate

View all literature mentions

VRC01 antibody (antibody)

RRID:AB_2491019

This monoclonal targets HIV-1 Envelope CD4 binding site

View all literature mentions

CD3e (antibody)

RRID:AB_394082

This monoclonal targets CD3e

View all literature mentions

VRC-PG04 antibody (antibody)

RRID:AB_2491022

This monoclonal targets HIV-1 Envelope CD4 binding site

View all literature mentions

VRC-CH31 antibody (antibody)

RRID:AB_2491024

This monoclonal targets HIV-1 Envelope CD4 binding site

View all literature mentions

CD8a (antibody)

RRID:AB_394081

This monoclonal targets CD8a

View all literature mentions

Expi293F (cell line)

RRID:CVCL_D615

Cell line Expi293F is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

View all literature mentions