Evidence map›Paper›PMID 29109276›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains.

Seth J Zost, Kaela Parkhouse, Megan E Gumina, Kangchon Kim, Sebastian Diaz Perez, Patrick C Wilson, John J Treanor, Andrea J Sant, Sarah Cobey, Scott E Hensley

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03734237 (A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD), which is not on this map. Cited by 360 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
360citing papers in PubMed, 3 pooled it
44.9field-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.

NCT03734237 phase4active not recruitingnot on this mapstarted 2018, after this paper: background citation

A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

TypeinterventionalSponsorHenry M. Jackson Foundation for the Advancement of Military MedicineRan2018 to 2026Enrolled15,448ConditionsInfluenza, Influenza-like Illness, Influenza VaccinesArmsEgg based influenza vaccines, Recombinant influenza vaccines, Cell-culture based influenza vaccines
3 · Its place in the literature

Who cites it

360 citing papers in PubMed, 3 syntheses or guidelines pooled it, 564 citations in OpenAlex.

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  7. Randomised immunogenicity trial comparing 2019-2020 recombinant and egg-based influenza vaccines among frequently vaccinated healthcare personnel in Israel.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2024
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  8. Preliminary Findings From the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: A Randomized Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
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300 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Seth J ZostDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Kaela ParkhouseDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Megan E GuminaDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Kangchon KimDepartment of Ecology and Evolution, University of Chicago, Chicago, IL 60637.
Sebastian Diaz PerezDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Patrick C WilsonDepartment of Medicine, University of Chicago, Chicago, IL 60637.
John J TreanorDepartment of Medicine, University of Rochester Medical Center, Rochester, NY 14642.
Andrea J SantDepartment of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642.
Sarah CobeyDepartment of Ecology and Evolution, University of Chicago, Chicago, IL 60637.
Scott E HensleyDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; hensley@pennmedicine.upenn.edu.ORCID 0000-0002-2928-7506
University of Pennsylvania · USUniversity of Chicago · USUniversity of Rochester Medical Center · US

Funding

VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGEDU19AI057266 · NIAID · EMORY UNIVERSITY · PI Rafi Ahmed · 2003 to 2026
$81.7M
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
University of Chicago Autoimmunity Center of ExcellenceU19AI082724 · NIAID · UNIVERSITY OF CHICAGO · PI CLARK, MARCUS RAMSAY · 2009 to 2023
$7.2M
TRAINING IN VIROLOGYT32AI007324 · NIAID · WISTAR INSTITUTE · PI Paul Bates, Matthew D. Weitzman · 1989 to 2026
$6.8M
Impact of prior influenza exposures on antibody repertoires to new viral strainsR01AI108686 · NIAID · WISTAR INSTITUTE · PI HENSLEY, SCOTT ERIC · 2014 to 2022
$3.7M
The effect of human pre-exposure history on antigenic drift of influenza virusesR01AI113047 · NIAID · WISTAR INSTITUTE · PI HENSLEY, SCOTT ERIC · 2014 to 2018
$2.5M
Modeling the Evolutionary Dynamics of Immunity to Influenza for Vaccine DevelopmeDP2AI117921 · NIAID · UNIVERSITY OF CHICAGO · PI COBEY, SARAH · 2014 to 2014
$2.1M
NIAID NIH HHS DP2 AI117921NIAID NIH HHS HHSN272201400005CNIAID NIH HHS R01 AI108686NIAID NIH HHS R01 AI113047NIAID NIH HHS T32 AI007324NIAID NIH HHS U19 AI057266NIAID NIH HHS U19 AI082724NIAID NIH HHS U19 AI109946
6 · The paper itself

Abstract

H3N2 viruses continuously acquire mutations in the hemagglutinin (HA) glycoprotein that abrogate binding of human antibodies. During the 2014-2015 influenza season, clade 3C.2a H3N2 viruses possessing a new predicted glycosylation site in antigenic site B of HA emerged, and these viruses remain prevalent today. The 2016-2017 seasonal influenza vaccine was updated to include a clade 3C.2a H3N2 strain; however, the egg-adapted version of this viral strain lacks the new putative glycosylation site. Here, we biochemically demonstrate that the HA antigenic site B of circulating clade 3C.2a viruses is glycosylated. We show that antibodies elicited in ferrets and humans exposed to the egg-adapted 2016-2017 H3N2 vaccine strain poorly neutralize a glycosylated clade 3C.2a H3N2 virus. Importantly, antibodies elicited in ferrets infected with the current circulating H3N2 viral strain (that possesses the glycosylation site) and humans vaccinated with baculovirus-expressed H3 antigens (that possess the glycosylation site motif) were able to efficiently recognize a glycosylated clade 3C.2a H3N2 virus. We propose that differences in glycosylation between H3N2 egg-adapted vaccines and circulating strains likely contributed to reduced vaccine effectiveness during the 2016-2017 influenza season. Furthermore, our data suggest that influenza virus antigens prepared via systems not reliant on egg adaptations are more likely to elicit protective antibody responses that are not affected by glycosylation of antigenic site B of H3N2 HA.

Indexed as

AnimalsAntibodies, ViralAntigens, ViralChickensFerretsGlycosylationHemagglutinin Glycoproteins, Influenza VirusHumansImmunogenicity, VaccineInfluenza A Virus, H3N2 SubtypeInfluenza, HumanInfluenza VaccinesMutationNeutralization TestsOvumAntibodies, ViralAntigens, ViralHemagglutinin Glycoproteins, Influenza VirusInfluenza Vaccinesantibodyhemagglutinininfluenzavaccine

Identifiers

PMID29109276
PMCPMC5703309
OpenAlexW2767495920

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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.