Evidence map›Paper›PMID 33951425›Full record

ArticleCell reports2021

Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies.

Emilie Seydoux, Yu-Hsin Wan, Junli Feng, Abigail Wall, Safia Aljedani, Leah J Homad, Anna J MacCamy, Connor Weidle, Matthew D Gray, Lauren Brumage and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Emilie SeydouxFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Yu-Hsin WanFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Junli FengFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Abigail WallFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Safia AljedaniFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Leah J HomadFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Anna J MacCamyFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Connor WeidleFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Matthew D GrayFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Lauren BrumageFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Justin J TaylorFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98195, USA; University of Washington, Department of Immunology, Seattle, WA 98109, USA.
Marie PanceraFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA.
Leonidas StamatatosFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98195, USA. Electronic address: lstamata@fredhutch.org.
Andrew T McGuireFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98195, USA. Electronic address: amcguire@fredhutch.org.
Fred Hutch Cancer Center · USUniversity of Washington · USInfectious Disease Research Institute · US

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Ritimukta Sarangi · 2020 to 2026
$43.3M
Recombinant HIV-1 Env glycoprotein immunogens and antibodies production and structural characterizationP01AI138212 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MCGUIRE, ANDREW · 2019 to 2023
$9.2M
Monitoring the development of anti-Env Abs during HIV infectionR01AI081625 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2010 to 2020
$5.8M
Identification and Analysis of HIV-specific Naive B cells in HIV-unexposed IndividualsR01AI122912 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TAYLOR, JUSTIN J · 2016 to 2020
$2.7M
Pilatus 6mS10OD021832 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ADAMS, PAUL DAVID · 2016 to 2016
$980k
Germline-targeting anti-idiotype antibodies as novel HIV-1 immunogensR21AI127249 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MCGUIRE, ANDREW · 2016 to 2017
$484k
NIAID NIH HHS P01 AI138212NIAID NIH HHS R01 AI081625NIAID NIH HHS R01 AI122912NIAID NIH HHS R21 AI127249NIGMS NIH HHS P30 GM133894NIH HHS S10 OD021832
6 · The paper itself

Abstract

An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several HIV-1 envelope-derived germline-targeting immunogens have been designed to engage naive VRC01-class precursor B cells. However, they also present off-target epitopes that could hinder development of VRC01-class bNAbs. We characterize a panel of anti-idiotypic monoclonal antibodies (ai-mAbs) raised against inferred-germline (iGL) VRC01-class antibodies. By leveraging binding, structural, and B cell sorting data, we engineered a bispecific molecule derived from two ai-mAbs; one specific for VRC01-class heavy chains and one specific for VRC01-class light chains. The bispecific molecule preferentially activates iGL-VRC01 B cells in vitro and induces specific antibody responses in a murine adoptive transfer model with a diverse polyclonal B cell repertoire. This molecule represents an alternative non-envelope-derived germline-targeting immunogen that can selectively activate VRC01-class precursors in vivo.

Indexed as

AIDS VaccinesAnimalsGerm CellsHIV-1HIV AntibodiesHumansMiceAIDS VaccinesHIV Antibodiesantibody heavy chainantibody light chainanti-idiotypic antibodiesB cell receptorbroadly neutralizing antibodiesHIV-1vaccines

Identifiers

PMID33951425
PMCPMC8127986
OpenAlexW3158982080

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.