Evidence map›Paper›PMID 32661157›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Adjuvanted H5N1 influenza vaccine enhances both cross-reactive memory B cell and strain-specific naive B cell responses in humans.

Ali H Ellebedy, Raffael Nachbagauer, Katherine J L Jackson, Ya-Nan Dai, Julianna Han, Wafaa B Alsoussi, Carl W Davis, Daniel Stadlbauer, Nadine Rouphael, Veronika Chromikova and 18 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

55 citing papers in PubMed, 87 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

28 authors at 5 institutions in 1 country.

Ali H EllebedyEmory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322.
Raffael NachbagauerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.ORCID 0000-0001-5568-5420
Katherine J L JacksonDepartment of Pathology, Stanford University, Stanford, CA 94305.
Ya-Nan DaiDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Julianna HanDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
Wafaa B AlsoussiDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Carl W DavisEmory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322.
Daniel StadlbauerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Nadine RouphaelDivision of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA 30322.
Veronika ChromikovaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Megan McCauslandEmory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322.
Cathy Y ChangEmory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322.
Mario CorteseDepartment of Pathology, School of Medicine, Emory University, Atlanta, GA 30322.
Mary BowerDivision of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA 30322.
Chakravarthy ChennareddyEmory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322.
Aaron J SchmitzDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Veronika I ZarnitsynaDepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322.
Lilin LaiDivision of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA 30322.
Arvind RajabhathorDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Cheyann KazemianEmory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322.
Rustom AntiaDepartment of Biology, Emory University, Atlanta, GA 30322.
Mark J MulliganDivision of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA 30322.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0001-7153-3769
Daved H FremontDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0002-8544-2689
Scott D BoydDepartment of Pathology, Stanford University, Stanford, CA 94305.
Bali PulendranEmory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322.
Florian KrammerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Rafi AhmedEmory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322; rahmed@emory.edu.
Emory University · USIcahn School of Medicine at Mount Sinai · USWashington University in St. Louis · USScripps Research Institute · USStanford University · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Systems Biological Analysis of Innate and Adaptive Responses to VaccinationU19AI090023 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, LI, SHUZHAO · 2010 to 2021
$45.0M
Toward a Universal Influenza Virus VaccineP01AI097092 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GARCIA-SASTRE, ADOLFO · 2012 to 2022
$17.6M
Understanding Human B Cell Responses to Influenza to Improve the Influenza U19AI109946 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI RAVETCH, JEFFREY VICTOR · 2014 to 2018
$9.6M
PATHOGENESIS AND IMMUNOLOGY OF DISEASET32AI007244 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 1985 to 2022
$8.8M
ALABAMA/ZAMBIA HIV VACCINE CLINICAL TRIALS UNIT (HVTU)U01AI047996 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GOEPFERT, PAUL A. · 2000 to 2006
$8.4M
Modeling the dynamics and evolution of immune responses to influenza virusesU19AI117891 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, ANTIA, RUSTOM NOSHIR · 2015 to 2019
$8.4M
Programming Durable Immune Responses To VaccinationU01AI141990 · NIAID · WASHINGTON UNIVERSITY · PI Ali Hassan Ellebedy · 2019 to 2026
$5.3M
MICROBES, DENDRITIC CELL SUBSETS AND T-CELL IMMUNITYR01AI048638 · NIAID · STANFORD UNIVERSITY · PI PULENDRAN, BALI · 2001 to 2024
$4.5M
Effects of aging on primary and secondary vaccine responses in a 15-year longitudinal cohortR01AI130398 · NIAID · STANFORD UNIVERSITY · PI BOYD, SCOTT DEXTER · 2017 to 2021
$4.0M
FUNCTIONAL ANALYSIS OF PATHOGENIC AND PROTECTIVE PEANUT ALLERGEN-SPECIFIC HUMAN ANTIBODIESR01AI125567 · NIAID · STANFORD UNIVERSITY · PI BOYD, SCOTT DEXTER · 2017 to 2022
$2.6M
Storage and recall of human B cell memory of influenza over tissues and timeR01AI127877 · NIAID · STANFORD UNIVERSITY · PI BOYD, SCOTT DEXTER · 2017 to 2021
$2.0M
NIAID NIH HHS HHSN272201400004CNIAID NIH HHS HHSN272201400008CNIAID NIH HHS P01 AI097092NIAID NIH HHS R01 AI048638NIAID NIH HHS R01 AI125567NIAID NIH HHS R01 AI127877NIAID NIH HHS R01 AI130398NIAID NIH HHS R21 AI139813NIAID NIH HHS R38 AI140299NIAID NIH HHS T32 AI007244NIAID NIH HHS U01 AI047996NIAID NIH HHS U01 AI141990NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI090023NIAID NIH HHS U19 AI109946NIAID NIH HHS U19 AI117891
6 · The paper itself

Abstract

There is a need for improved influenza vaccines. In this study we compared the antibody responses in humans after vaccination with an AS03-adjuvanted versus nonadjuvanted H5N1 avian influenza virus inactivated vaccine. Healthy young adults received two doses of either formulation 3 wk apart. We found that AS03 significantly enhanced H5 hemagglutinin (HA)-specific plasmablast and antibody responses compared to the nonadjuvanted vaccine. Plasmablast response after the first immunization was exclusively directed to the conserved HA stem region and came from memory B cells. Monoclonal antibodies (mAbs) derived from these plasmablasts had high levels of somatic hypermutation (SHM) and recognized the HA stem region of multiple influenza virus subtypes. Second immunization induced a plasmablast response to the highly variable HA head region. mAbs derived from these plasmablasts exhibited minimal SHM (naive B cell origin) and largely recognized the HA head region of the immunizing H5N1 strain. Interestingly, the antibody response to H5 HA stem region was much lower after the second immunization, and this suppression was most likely due to blocking of these epitopes by stem-specific antibodies induced by the first immunization. Taken together, these findings show that an adjuvanted influenza vaccine can substantially increase antibody responses in humans by effectively recruiting preexisting memory B cells as well as naive B cells into the response. In addition, we show that high levels of preexisting antibody can have a negative effect on boosting. These findings have implications toward the development of a universal influenza vaccine.

Indexed as

Adjuvants, ImmunologicImmunologic MemoryAntibodies, ViralAntibody FormationAntibody SpecificityB-LymphocytesCross ReactionsEpitopes, B-LymphocyteFemaleHumansImmunization, SecondaryInfluenza A Virus, H5N1 SubtypeInfluenza, HumanInfluenza VaccinesMalePlasma CellsAdjuvants, ImmunologicAntibodies, ViralEpitopes, B-LymphocyteInfluenza VaccinesadjuvantB cellsH5N1influenzamemory

Identifiers

PMID32661157
PMCPMC7395544
OpenAlexW3041479707

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.