Evidence map›Paper›PMID 36629414›Full record

ArticlemBio2023

A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.

Frederic Bibollet-Ruche, Ronnie M Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N Skelly, Ryan S Roark and 34 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 20% 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, 10 citations in OpenAlex.

  1. Deletions in variable region 1 of the HIV envelope accelerate V3-glycan bNAb induction in SHIV-infected rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

44 authors at 9 institutions in 2 countries.

Frederic Bibollet-Ruche *Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ronnie M Russell *Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Wenge Ding *Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Weimin Liu *Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Yingying Li *Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kshitij WaghTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Daniel WrappDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.ORCID 0000-0002-0538-9647
Rumi HabibDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ashwin N SkellyDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-1565-3376
Ryan S RoarkDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Scott Sherrill-MixDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Shuyi WangDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Juliette RandoDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Emily LindemuthDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kendra CruickshankDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Younghoon ParkDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Rachel BaumDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
John W CareyDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Andrew Jesse ConnellDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Hui LiDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Elena E GiorgiTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Ge S SongDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.
Shilei DingCentre de Recherche du CHUM, Montreal, Quebec, Canada.
Andrés FinziCentre de Recherche du CHUM, Montreal, Quebec, Canada.ORCID 0000-0002-4992-5288
Amanda NewmanDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Giovanna E HernandezDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Emily MachieleDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Derek W CainDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Katayoun MansouriDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Mark G LewisBioqual, Inc., Rockville, Maryland, USA.
David C MontefioriDepartment of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Kevin J WieheDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
S Munir AlamDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.ORCID 0000-0003-0941-0703
I-Ting TengVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0003-3560-232X
Raiees AndrabiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.
Laurent VerkoczySan Diego Biomedical Research Institute, San Diego, California, USA.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.
Bette T KorberTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Kevin O SaundersDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Robert J EdwardsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
George M ShawDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-2338-4532
Beatrice H HahnDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-9400-9887
University of Pennsylvania · USDuke University · USLos Alamos National Laboratory · USScripps Research Institute · USCentre Hospitalier de l’Université de Montréal · CANational Institutes of Health · USThe Wistar Institute · USBioqual · USSan Diego Biomedical Research Institute · US

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Nonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
Viral TestingU42OD021458 · OD · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI Armando Gil Burgos-Rodriguez, Marcos Lopez · 2016 to 2026
$45.1M
Virus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7M
Translational Science InitiativeP40OD012217 · OD · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI CARLOS A SARIOL · 2012 to 2026
$40.4M
Design Of ImmunogensZIAAI005024 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$21.5M
TRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6M
Ruth L. Kirschstein National Research Service Award (NRSA)- T32T32AI007392 · NIAID · DUKE UNIVERSITY · PI Amy Lynn Corneli, Guido Ferrari · 1990 to 2026
$9.8M
Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogensR37AI150590 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Beatrice H Hahn · 2019 to 2026
$6.9M
HIV-1 Q23.17 Env: Engineering a novel immunogen to elicit broadly neutralizing antibodiesR01AI165080 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GEORGE M SHAW · 2021 to 2026
$6.6M
Natural SIV Reservoirs and Human Zoonotic RiskR01AI050529 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2001 to 2022
$6.1M
NIAID NIH HHS P01 AI131251NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI050529NIAID NIH HHS R01 AI087202NIAID NIH HHS R01 AI141338NIAID NIH HHS R01 AI160607NIAID NIH HHS R01 AI165080NIAID NIH HHS R01 AI167716NIAID NIH HHS R37 AI150590NIAID NIH HHS R61 AI161818NIAID NIH HHS T32 AI007392NIAID NIH HHS T32 AI007632NIAID NIH HHS UM1 AI144371NIAID NIH HHS UM1 AI144462NIH HHS P40 OD012217NIH HHS U42 OD021458
6 · The paper itself

Abstract

HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in human V2-apex bNAb heavy-chain precursor-expressing knock-in mice and as chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) in rhesus macaques (RMs). Trimer immunization of knock-in mice induced V2-directed NAbs, indicating activation of V2-apex bNAb precursor-expressing mouse B cells. SCIV infection of RMs elicited high-titer viremia, potent autologous tier 2 neutralizing antibodies, and rapid sequence escape in the canonical V2-apex epitope. Six of seven animals also developed low-titer heterologous plasma breadth that mapped to the V2-apex. Antibody cloning from two of these animals identified multiple expanded lineages with long heavy chain third complementarity determining regions that cross-neutralized as many as 7 of 19 primary HIV-1 strains, but with low potency. Negative stain electron microscopy (NSEM) of members of the two most cross-reactive lineages confirmed V2 targeting but identified an angle of approach distinct from prototypical V2-apex bNAbs, with antibody binding either requiring or inducing an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency.

Indexed as

HIV-1HIV InfectionsAnimalsAntibodies, NeutralizingBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusEpitopesGlycoproteinsHIV AntibodiesHumansMacaca mulattaMicePan troglodytesAntibodies, NeutralizingBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusEpitopesGlycoproteinsHIV Antibodiesbroadly neutralizing antibodieschimpanzeegermline-targetinghuman immunodeficiency virusimmunofocusingneutralizing antibodiesoccluded-open trimerSCIVV2-apexvaccines

Identifiers

PMID36629414
PMCPMC9973348
OpenAlexW4315619806

What OpenQuestion holds

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Registered trials

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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.