Evidence map›Paper›PMID 33556148›Full record

ArticlePLoS pathogens2021

The C3/465 glycan hole cluster in BG505 HIV-1 envelope is the major neutralizing target involved in preventing mucosal SHIV infection.

Tysheena P Charles, Samantha L Burton, Prabhu S Arunachalam, Christopher A Cottrell, Leigh M Sewall, Venkata S Bollimpelli, Sailaja Gangadhara, Antu K Dey, Andrew B Ward, George M Shaw and 5 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

29 citing papers in PubMed, 35 citations in OpenAlex.

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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

15 authors at 6 institutions in 2 countries.

Tysheena P CharlesEmory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.
Samantha L BurtonEmory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.
Prabhu S ArunachalamDepartments of Pathology, and Microbiology and Immunology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0003-0090-5689
Christopher A CottrellDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0002-3364-3083
Leigh M SewallDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0002-2020-2991
Venkata S BollimpelliEmory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.
Sailaja GangadharaEmory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.ORCID 0000-0001-8603-628X
Antu K DeyInternational AIDS Vaccine Initiative, New York, New York, United States of America.ORCID 0000-0001-7438-9379
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0001-7153-3769
George M ShawDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Eric HunterEmory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.ORCID 0000-0002-4273-8631
Rama R AmaraEmory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.ORCID 0000-0002-6309-6797
Bali PulendranDepartments of Pathology, and Microbiology and Immunology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0001-6517-4333
Marit J van GilsDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0003-3422-8161
Cynthia A DerdeynEmory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.ORCID 0000-0002-1220-513X
Emory University · USScripps Research Institute · USStanford University · USAmsterdam University Medical Centers · NLInternational AIDS Vaccine Initiative · USUniversity of Pennsylvania · 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
Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0M
B and T Cell Biology of Protection from and Eradication of SIV/SHIV Infection - Administrative SupplementUM1AI124436 · NIAID · EMORY UNIVERSITY · PI AMARA, RAMA RAO, HUNTER, ERIC · 2016 to 2021
$42.3M
Virus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GEORGE M SHAW · 2017 to 2026
$40.7M
B and T Cell Biology of Protection from and Eradication of SIV/SHIV InfectionUM1AI169662 · NIAID · EMORY UNIVERSITY · PI Rama Rao Amara, Eric Hunter · 2022 to 2026
$32.0M
Viral Testing Core-Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research CenterU42OD011023 · OD · EMORY UNIVERSITY · PI Matthew Ryan Gardner · 2018 to 2026
$17.5M
Role of V1V2 in HIV transmission and pathogenesisR01AI058706 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DERDEYN, CYNTHIA ANN · 2004 to 2016
$6.7M
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
Using DNA/MVA/protein immunization of rhesus macaques to investigate how the background of the HIV-1 envelope and nature of the protein boost shape the genetic and functional antibody landscape.R01AI128837 · NIAID · EMORY UNIVERSITY · PI BOSINGER, STEVEN EDWARD, DERDEYN, CYNTHIA ANN · 2017 to 2021
$5.9M
Combining germline-targeting, B cell immunofocusing and Env-Ab coevolution strategies to induce HIV Envelope V2-apex broadly neutralizing antibodiesR61AI161818 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ANDRABI, RAIEES AHMAD, SHAW, GEORGE M · 2021 to 2023
$4.7M
Reverse Vaccinology in SHIV Infected Macaques as a Molecular Guide for HIV-1 Vaccine DesignR01AI160607 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI SHAW, GEORGE M · 2021 to 2024
$3.2M
NIAID NIH HHS F31 AI131873NIAID NIH HHS P01 AI131251NIAID NIH HHS P30 AI050409NIAID NIH HHS R01 AI058706NIAID NIH HHS R01 AI128837NIAID NIH HHS R01 AI160607NIAID NIH HHS R01 AI165080NIAID NIH HHS R21 AI150292NIAID NIH HHS R61 AI161818NIAID NIH HHS UM1 AI124436NIAID NIH HHS UM1 AI144462NIAID NIH HHS UM1 AI169662NIH HHS P51 OD011132NIH HHS U42 OD011023
6 · The paper itself

Abstract

Stabilized HIV-1 envelope (Env) trimers elicit tier 2 autologous neutralizing antibody (nAb) responses in immunized animals. We previously demonstrated that BG505 SOSIP.664.T332N gp140 (BG505 SOSIP) immunization of rhesus macaques (RM) provided robust protection against autologous intra-vaginal simian-human immunodeficiency virus (SHIV) challenge that was predicted by high serum nAb titers. Here, we show that nAb in these protected RM targeted a glycan hole proximal to residue 465 in gp120 in all cases. nAb also targeted another glycan hole at residues 241/289 and an epitope in V1 at varying frequencies. Non-neutralizing antibodies directed at N611-shielded epitopes in gp41 were also present but were more prevalent in RM with low nAb titers. Longitudinal analysis demonstrated that nAb broadened in some RM during sequential immunization but remained focused in others, the latter being associated with increases in nAb titer. Thirty-eight monoclonal antibodies (mAbs) isolated from a protected RM with an exceptionally high serum neutralization titer bound to the trimer in ELISA, and four of the mAbs potently neutralized the BG505 Env pseudovirus (PV) and SHIV. The four neutralizing mAbs were clonally related and targeted the 465 glycan hole to varying degrees, mimicking the serum. The data demonstrate that the C3/465 glycan hole cluster was the dominant neutralization target in high titer protected RM, despite other co-circulating neutralizing and non-neutralizing specificities. The isolation of a neutralizing mAb family argues that clonotype expansion occurred during BG505 SOSIP immunization, leading to high titer, protective nAb and setting a desirable benchmark for HIV vaccines.

Indexed as

AnimalsAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesFemaleHIV-1HIV AntibodiesHIV InfectionsHumansImmunizationMacaca mulattaPolysaccharidesSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusVaccinationAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesPolysaccharides

Identifiers

PMID33556148
PMCPMC7895394
OpenAlexW3126244679

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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.