Evidence map›Paper›PMID 33438580›Full record

ArticleeLife2021

High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination.

Adam S Dingens, Payal Pratap, Keara Malone, Sarah K Hilton, Thomas Ketas, Christopher A Cottrell, Julie Overbaugh, John P Moore, P J Klasse, Andrew B Ward and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 31 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

11 authors at 4 institutions in 1 country.

Adam S DingensBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, United States.ORCID 0000-0001-9603-9409
Payal PratapDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States.ORCID 0000-0002-7170-6866
Keara MaloneBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, United States.
Sarah K HiltonBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, United States.
Thomas KetasDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, United States.
Christopher A CottrellDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States.
Julie OverbaughHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States.ORCID 0000-0002-0239-9444
John P MooreDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, United States.
P J KlasseDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, United States.ORCID 0000-0001-8222-278X
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States.ORCID 0000-0001-7153-3769
Jesse D BloomBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, United States.ORCID 0000-0003-1267-3408
Fred Hutch Cancer Center · USCornell University · USScripps Research Institute · USHoward Hughes Medical Institute · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Mitchell Smith · 1994 to 2026
$78.4M
Structural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4M
Neutralization of Primate Immunodeficiency VirusesR01AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN P MOORE · 1994 to 2026
$4.3M
Complete mapping of immune selection from antibodies to HIVR01AI140891 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BLOOM, JESSE D · 2019 to 2024
$2.4M
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001442NIAID NIH HHS P01 AI110657NIAID NIH HHS P30 AI036214NIAID NIH HHS R01 AI036082NIAID NIH HHS R01 AI140891
6 · The paper itself

Abstract

Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.

Indexed as

Epitope MappingAIDS VaccinesAnimalsenv Gene Products, Human Immunodeficiency VirusHIV-1HIV AntibodiesRabbitsAIDS Vaccinesenv Gene Products, Human Immunodeficiency VirusHIV Antibodieselectron microscopy polyclonal epitope mappingEnv trimer immunizationHIVimmunologyinfectious diseaseinflammationmicrobiologymutational antigenic profilingpolyclonal seravirus

Identifiers

PMID33438580
PMCPMC7864656
OpenAlexW3118647339

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.