Evidence map›Paper›PMID 27312086›Full record

ArticleGenome medicine2016

B-cell repertoire dynamics after sequential hepatitis B vaccination and evidence for cross-reactive B-cell activation.

Jacob D Galson, Johannes Trück, Elizabeth A Clutterbuck, Anna Fowler, Vincenzo Cerundolo, Andrew J Pollard, Gerton Lunter, Dominic F Kelly

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Genome medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
6.9field-weighted citation impact, top 3% 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

45 citing papers in PubMed, 73 citations in OpenAlex.

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  5. Dynamics of memory B cells and plasmablasts in healthy individuals.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  9. Computational detection of antigen-specific B cell receptors following immunization.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  19. Human immune repertoire in hepatitis B virus infection.World journal of gastroenterology · 2021
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Jacob D GalsonOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, OX3 7LE, UK. jacob.galson@paediatrics.ox.ac.uk.
Johannes TrückOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, OX3 7LE, UK.
Elizabeth A ClutterbuckOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, OX3 7LE, UK.
Anna FowlerWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Vincenzo CerundoloMedical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK.
Andrew J PollardOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, OX3 7LE, UK.
Gerton LunterWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Dominic F KellyOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, OX3 7LE, UK.
University of Oxford · GBCentre for Human Genetics · GBMedical Research Council · GBOxford BioMedica (United Kingdom) · GB

Funding

Cancer Research UK 17722Medical Research Council G1000800Medical Research Council MC_UU_12010/1Wellcome Trust
6 · The paper itself

Abstract

backgroundA diverse B-cell repertoire is essential for recognition and response to infectious and vaccine antigens. High-throughput sequencing of B-cell receptor (BCR) genes can now be used to study the B-cell repertoire at great depth and may shed more light on B-cell responses than conventional immunological methods. Here, we use high-throughput BCR sequencing to provide novel insight into B-cell dynamics following a primary course of hepatitis B vaccination.

methodsNine vaccine-naïve participants were administered three doses of hepatitis B vaccine (months 0, 1, and 2 or 7). High-throughput Illumina sequencing of the total BCR repertoire was combined with targeted sequencing of sorted vaccine antigen-enriched B cells to analyze the longitudinal response of both the total and vaccine-specific repertoire after each vaccine. ELISpot was used to determine vaccine-specific cell numbers following each vaccine.

resultsDeconvoluting the vaccine-specific from total BCR repertoire showed that vaccine-specific sequence clusters comprised <0.1 % of total sequence clusters, and had certain stereotypic features. The vaccine-specific BCR sequence clusters were expanded after each of the three vaccine doses, despite no vaccine-specific B cells being detected by ELISpot after the first vaccine dose. These vaccine-specific BCR clusters detected after the first vaccine dose had distinct properties compared to those detected after subsequent doses; they were more mutated, present at low frequency even prior to vaccination, and appeared to be derived from more mature B cells.

conclusionsThese results demonstrate the high-sensitivity of our vaccine-specific BCR analysis approach and suggest an alternative view of the B-cell response to novel antigens. In the response to the first vaccine dose, many vaccine-specific BCR clusters appeared to largely derive from previously activated cross-reactive B cells that have low affinity for the vaccine antigen, and subsequent doses were required to yield higher affinity B cells.

Indexed as

AdultB-LymphocytesHealthy VolunteersHepatitis B VaccinesHigh-Throughput Nucleotide SequencingHumansLongitudinal StudiesLymphocyte ActivationReceptors, Antigen, B-CellSequence Analysis, DNAYoung AdultHepatitis B VaccinesReceptors, Antigen, B-CellAntibodyB-cell repertoireHepatitis BPolyreactiveVaccinationVDJ

Identifiers

PMID27312086
PMCPMC4910312
OpenAlexW2441069795

What OpenQuestion holds

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LicenceCC BY
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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.