Evidence map›Paper›PMID 39667375›Full record

Observational studyThe Lancet. Microbe2025

Molecular features of the serological IgG repertoire elicited by egg-based, cell-based, or recombinant haemagglutinin-based seasonal influenza vaccines: a comparative, prospective, observational cohort study.

Juyeon Park, Foteini Bartzoka, Troy von Beck, Zhu-Nan Li, Margarita Mishina, Luke S Hebert, Jessica Kain, Feng Liu, Suresh Sharma, Weiping Cao and 24 more

Abstract readObservational StudyComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Lancet. Microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

34 authors.

Juyeon ParkDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Foteini BartzokaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Troy von BeckDepartment of Microbiology and Immunology, Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA, USA.
Zhu-Nan LiCenters for Disease Control and Prevention, Atlanta, GA, USA.
Margarita MishinaCenters for Disease Control and Prevention, Atlanta, GA, USA.
Luke S HebertDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Jessica KainDepartment of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Feng LiuCenters for Disease Control and Prevention, Atlanta, GA, USA.
Suresh SharmaCenters for Disease Control and Prevention, Atlanta, GA, USA.
Weiping CaoCenters for Disease Control and Prevention, Atlanta, GA, USA.
Devon J EddinsCenters for Disease Control and Prevention, Atlanta, GA, USA.
Amrita KumarCenters for Disease Control and Prevention, Atlanta, GA, USA.
Jin Eyun KimDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Justin S LeeCenters for Disease Control and Prevention, Atlanta, GA, USA.
Yuanyuan WangCenters for Disease Control and Prevention, Atlanta, GA, USA.
Evan A SchwartzSauer Structural Biology Laboratory, Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX, USA.
Axel F BrilotSauer Structural Biology Laboratory, Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX, USA.
Ed SatterwhiteDepartment of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Dalton M TowersDepartment of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Eric McKnightDepartment of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Jan PohlCenters for Disease Control and Prevention, Atlanta, GA, USA.
Mark G ThompsonCenters for Disease Control and Prevention, Atlanta, GA, USA.
Manjusha GaglaniBaylor Scott & White Health, Baylor College of Medicine and Texas A&M University College of Medicine, Temple, TX, USA.
Fatimah S DawoodCenters for Disease Control and Prevention, Atlanta, GA, USA.
Allison L NalewayKaiser Permanente Center for Health Research, Portland, OR, USA.
James StevensCenters for Disease Control and Prevention, Atlanta, GA, USA.
Richard B KennedyDepartment of Medicine, Mayo Clinic, Rochester, MN, USA.
Joshy JacobDepartment of Microbiology and Immunology, Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA, USA.
Jason J LavinderDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Min Z LevineCenters for Disease Control and Prevention, Atlanta, GA, USA.
Shivaprakash GangappaCenters for Disease Control and Prevention, Atlanta, GA, USA.
Gregory C IppolitoDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Suryaprakash SambharaCenters for Disease Control and Prevention, Atlanta, GA, USA.
George GeorgiouDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA. Electronic address: gg@che.utexas.edu.

Funding

COVID Supplement - COMPONENT A OF THE COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTERS (CIVICS) PROGRAM TO DESIGN AND EVALUATE INNOVATIVE INFLUENZA VACCINE APPROACHES,75N93019C00052 · NIAID · UNIVERSITY OF GEORGIA · PI ROSS, TED · 2019 to 2025
$74.6M
Collaborative Influenza Vaccine Innovation Centers (CIVICs): Component A: Vaccine Center75N93019C00050 · NIAID · DUKE UNIVERSITY · PI MOODY, TONY · 2019 to 2025
$69.1M
CDC HHSGates Foundation INV-004956NIAID NIH HHS 75N93019C00050NIAID NIH HHS 75N93019C00052
6 · The paper itself

Abstract

backgroundEgg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response.

methodsIn this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA). Eligible individuals were selected based on comparable day 28 serum microneutralisation titres and similar vaccination history. Laboratory investigators were blinded to assignment until testing was completed. The preplanned exploratory endpoints were assessed by deconvoluting the serological repertoire specific to A/Singapore/INFIMH-16-0019/2016 (H3N2) HA before (day 0) and after (day 28) immunisation using bottom-up liquid chromatography-mass spectrometry proteomics (referred to as Ig-Seq) and natively paired variable heavy chain-variable light chain high-throughput B-cell receptor sequencing (referred to as BCR-Seq). Features of the antigen-specific serological repertoire at day 0 and day 28 for the three vaccine groups were compared. Antibodies identified with high confidence in sera were recombinantly expressed and characterised in depth to determine the binding affinity and breadth to time-ordered H3 HA proteins.

findingsDuring September and October of the 2018-19 influenza season, 15 individuals were recruited and assigned to receive RIV4 (n=5), eIIV4 (n=5), or ccIIV4 (n=5). For all three cohorts, the serum antibody repertoire was dominated by back-boosted antibody lineages (median 98% [95% CI 88-99]) that were present in the serum before vaccination. Although vaccine platform-dependent differences were not evident in the repertoire diversity, somatic hypermutation, or heavy chain complementarity determining region 3 biochemical features, antibodies boosted by RIV4 showed substantially higher binding affinity to the vaccine H3/HA (median half-maximal effective concentration [EC50] to A/Singapore/INFIMH-16-0019/2016 HA: 0·037 μg/mL [95% CI 0·012-0·12] for RIV4; 4·43 μg/mL [0·030-100·0] for eIIV4; and 18·50 μg/mL [0·99-100·0] μg/mL for ccIIV4) and also the HAs from contemporary H3N2 strains than did those elicited by eIIV4 or ccIIV4 (median EC50 to A/Texas/50/2012 HA: 0·037 μg/mL [0·017-0·32] for RIV4; 1·10 μg/mL [0·045-100] for eIIV4; and 12·6 μg/mL [1·8-100] for ccIIV4). Comparison of B-cell receptor sequencing repertoires on day 7 showed that eIIV4 increased the median frequency of canonical egg glycan-targeting B cells (0·20% [95% CI 0·067-0·37] for eIIV4; 0·058% [0·050-0·11] for RIV4; and 0·035% [0-0·062] for ccIIV4), whereas RIV4 vaccination decreased the median frequency of B-cell receptors displaying stereotypical features associated with membrane proximal anchor-targeting antibodies (0·062% [95% CI 0-0·084] for RIV4; 0·12% [0·066-0·16] for eIIV4; and 0·18% [0·016-0·20] for ccIIV4). In exploratory analysis, we characterised the structure of a highly abundant monoclonal antibody that binds to both group 1 and 2 HAs and recognises the HA trimer interface, despite its sequence resembling the stereotypical sequence motif found in membrane-proximal anchor binding antibodies.

interpretationAlthough all three licensed seasonal influenza vaccines elicit serological antibody repertoires with indistinguishable features shaped by heavy imprinting, the RIV4 vaccine selectively boosts higher affinity monoclonal antibodies to contemporary strains and elicits greater serum binding potency and breadth, possibly as a consequence of the multivalent structural features of the HA immunogen in this vaccine formulation. Collectively, our findings show advantages of RIV4 vaccines and more generally highlight the benefits of multivalent HA immunogens in promoting higher affinity serum antibody responses.

fundingCenters for Disease Control and Prevention, National Institutes of Health, and Bill & Melinda Gates Foundation.

Indexed as

Antibodies, ViralHemagglutinin Glycoproteins, Influenza VirusImmunoglobulin GInfluenza, HumanInfluenza VaccinesAdultFemaleHumansMiddle AgedProspective StudiesProteomicsSeasonsVaccinationVaccines, InactivatedAntibodies, ViralHemagglutinin Glycoproteins, Influenza VirusImmunoglobulin GInfluenza VaccinesVaccines, Inactivated

Identifiers

PMID39667375
PMCPMC11807745

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