Evidence map›Paper›PMID 34697307›Full record

ArticleNPJ vaccines2021

Antibody elicited by HIV-1 immunogen vaccination in macaques displaces Env fusion peptide and destroys a neutralizing epitope.

Morgan E Abernathy, Harry B Gristick, Jost Vielmetter, Jennifer R Keeffe, Priyanthi N P Gnanapragasam, Yu E Lee, Amelia Escolano, Rajeev Gautam, Michael S Seaman, Malcolm A Martin and 2 more

Open access · goldAbstract read
In one paragraph

Article in NPJ vaccines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

Morgan E AbernathyDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.ORCID http://orcid.org/0000-0001-9959-7713
Harry B GristickDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Jost VielmetterDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Jennifer R KeeffeDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.ORCID http://orcid.org/0000-0002-5317-6398
Priyanthi N P GnanapragasamDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Yu E LeeDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.ORCID http://orcid.org/0000-0001-5989-326X
Amelia EscolanoLaboratory of Molecular Immunology, New York, 10065, USA.
Rajeev GautamLaboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Malcolm A MartinLaboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-6845-9905
Michel C NussenzweigLaboratory of Molecular Immunology, New York, 10065, USA.ORCID http://orcid.org/0000-0003-0592-8564
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA. bjorkman@caltech.edu.ORCID http://orcid.org/0000-0002-2277-3990
California Institute of Technology · USNational Institutes of Health · USBeth Israel Deaconess Medical Center · USCenter for Molecular Medicine and Immunology · USHoward Hughes Medical Institute · US

Funding

Stuctural basis of bNab activityP01AI100148 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Pamela J Bjorkman · 2013 to 2026
$43.3M
Virus TransmissionP50AI150464 · NIAID · UNIVERSITY OF UTAH · PI HOPE, THOMAS · 2019 to 2021
$14.9M
Design of vaccination strategies to elicit broadly neutralizing antibodies against HIV-1R00AI140770 · NIAID · WISTAR INSTITUTE · PI ESCOLANO, AMELIA · 2021 to 2022
$498k
Design of vaccination strategies to elicit broadly neutralizing antibodies against HIV-1K99AI140770 · NIAID · ROCKEFELLER UNIVERSITY · PI ESCOLANO, AMELIA · 2019 to 2020
$262k
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) CAVD INV-002143Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) #OPP1146996Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) HIVRAD P01 AI100148Gates Foundation INV-002143NIAID NIH HHS K99 AI140770NIAID NIH HHS P01 AI100148NIAID NIH HHS P50 AI150464NIAID NIH HHS R00 AI140770
6 · The paper itself

Abstract

HIV-1 vaccine design aims to develop an immunogen that elicits broadly neutralizing antibodies against a desired epitope, while eliminating responses to off-target regions of HIV-1 Env. We report characterization of Ab1245, an off-target antibody against the Env gp120-gp41 interface, from V3-glycan patch immunogen-primed and boosted macaques. A 3.7 Å cryo-EM structure of an Ab1245-Env complex reveals one Ab1245 Fab binding asymmetrically to Env trimer at the gp120-gp41 interface using its long CDRH3 to mimic regions of gp41. The mimicry includes positioning of a CDRH3 methionine into the gp41 tryptophan clasp, resulting in displacement of the fusion peptide and fusion peptide-proximal region. Despite fusion peptide displacement, Ab1245 is non-neutralizing even at high concentrations, raising the possibility that only two fusion peptides per trimer are required for viral-host membrane fusion. These structural analyses facilitate immunogen design to prevent elicitation of Ab1245-like antibodies that block neutralizing antibodies against the fusion peptide.

Identifiers

PMID34697307
PMCPMC8545924
OpenAlexW3210061095

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.