Evidence map›Paper›PMID 27610569›Full record

ArticleCell2016

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.

Amelia Escolano, Jon M Steichen, Pia Dosenovic, Daniel W Kulp, Jovana Golijanin, Devin Sok, Natalia T Freund, Alexander D Gitlin, Thiago Oliveira, Tatsuya Araki and 12 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers.

0numbers the graph read from it
0cells of the map it votes in
242citing papers in PubMed
27.7field-weighted citation impact, top 1% 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

242 citing papers in PubMed, 342 citations in OpenAlex.

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  13. Clonal dynamics of germinal center refueling by secondary immunization.bioRxiv : the preprint server for biology · 2026
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  19. Nanoparticle Immunoadjuvant Complexes Augment Germinal Center Responses to Vaccination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  20. Article

182 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 5 institutions in 1 country.

Amelia EscolanoLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Jon M SteichenDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pia DosenovicLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Daniel W KulpDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jovana GolijaninLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Devin SokDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10004, USA.
Natalia T FreundLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Alexander D GitlinLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Thiago OliveiraLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Tatsuya ArakiLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Sarina LoweLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Spencer T ChenLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Jennifer HeinemannLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Kai-Hui YaoLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Erik GeorgesonDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Karen L Saye-FranciscoDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Anna GazumyanLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Yumiko AdachiDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Michael KubitzDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Dennis R BurtonDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
William R SchiefDepartment of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA. Electronic address: schief@scripps.edu.
Michel C NussenzweigLaboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA. Electronic address: nussen@rockefeller.edu.
Rockefeller University · USInternational AIDS Vaccine Initiative · USScripps Research Institute · USHoward Hughes Medical Institute · USRagon Institute of MGH, MIT and Harvard · US

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
Stuctural basis of bNab activityP01AI100148 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Pamela J Bjorkman · 2013 to 2026
$43.3M
Preclinical Evaluation of Envelope Immunogens Optimized to Elicit VRCOI-class AnU19AI109632 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2014 to 2020
$25.1M
Glycan dependent epitopes of HIV broadly neutralizing antibodiesR01AI113867 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C, SCHIEF, WILLIAM R. · 2014 to 2018
$4.8M
Immunity and Infectious DiseaseT32AI070084 · NIAID · ROCKEFELLER UNIVERSITY · PI Michel C Nussenzweig · 2008 to 2026
$3.3M
Howard Hughes Medical InstituteNIAID NIH HHS P01 AI100148NIAID NIH HHS R01 AI113867NIAID NIH HHS T32 AI070084NIAID NIH HHS U19 AI109632NIAID NIH HHS UM1 AI100663NIGMS NIH HHS T32 GM007739
6 · The paper itself

Abstract

A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2-neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data establish that sequential immunization with specifically designed immunogens can induce high levels of somatic mutation and shepherd antibody maturation to produce bNAbs from their inferred germline precursors.

Indexed as

ImmunizationAIDS VaccinesAmino Acid SequenceAnimalsAntibodies, NeutralizingAntigens, ViralB-LymphocytesCloning, MolecularDNA PrimersEpitopesGene Knock-In TechniquesHIV-1HIV AntibodiesHIV InfectionsImmunoglobulinsMiceAIDS VaccinesAntibodies, NeutralizingAntigens, ViralDNA PrimersEpitopesHIV AntibodiesImmunoglobulins

Identifiers

PMID27610569
PMCPMC5019122
OpenAlexW2515956381

What OpenQuestion holds

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LicenceTDM
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.