Evidence map›Paper›PMID 31481254›Full record

ArticleVaccine2019

Structural and antigenic characterization of a computationally-optimized H5 hemagglutinin influenza vaccine.

Yael Bar-Peled, Jiachen Huang, Ivette A Nuñez, Spencer R Pierce, Jeffrey W Ecker, Ted M Ross, Jarrod J Mousa

Open access · greenAbstract read
In one paragraph

Article in Vaccine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 20 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

7 authors at 1 institution in 1 country.

Yael Bar-PeledCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
Jiachen HuangCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
Ivette A NuñezCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
Spencer R PierceCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
Jeffrey W EckerCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
Ted M RossCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
Jarrod J MousaCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States. Electronic address: jarrod.mousa@uga.edu.
University of Georgia · US

Funding

Structural and mechanistic insights into antibody neutralization of human metapneumovirusR01AI143865 · NIAID · UNIVERSITY OF GEORGIA · PI MOUSA, JARROD · 2019 to 2023
$3.0M
Phase II SER-CAT Optimization: Acquisition of a next generation area detectorS10RR028976 · NCRR · UNIVERSITY OF GEORGIA · PI WANG, BI-CHENG · 2010 to 2010
$1.5M
Therapeutic antibodies to treat Pneumocystis pneumonia in a nonhuman primate model of HIV infectionK01OD026569 · OD · UNIVERSITY OF GEORGIA · PI MOUSA, JARROD · 2018 to 2020
$1.0M
Acquition of a microdiffractometer for SER-CATS10RR025528 · NCRR · UNIVERSITY OF GEORGIA · PI ROSE, JOHN PATRICK · 2009 to 2009
$414k
NCRR NIH HHS S10 RR025528NCRR NIH HHS S10 RR028976NIAID NIH HHS R01 AI143865NIH HHS K01 OD026569
6 · The paper itself

Abstract

Influenza A virus is a leading cause of death worldwide. Viruses of the H5 subtype have the potential to induce high mortality, and no vaccines are currently available to protect against H5 influenza viruses in the event of an outbreak. Experimental vaccination with one clade 2 virus does not protect against other subclades. The computationally optimized broadly reactive (COBRA) methodology was previously used to generate a H5 hemagglutinin (HA) antigen (COBRA2) that elicited increased serological breadth against multiple clade 2 H5N1 influenza viruses. In this report, we structurally and antigenically characterized the COBRA2 HA antigen. We examined the biochemical characteristics of the COBRA2 protein and determined the protein is correctly cleaved, properly folded into a trimeric structure, and antigenically correct by probing with HA head- and stem-specific monoclonal antibodies (mAbs). We further probed the antigenicity by examining binding of a panel of H5 mouse mAbs to the COBRA2 antigen, as well as several other HA antigens. We determined the X-ray crystal structure of the COBRA2 HA antigen to 2.8 Å and the protein was observed to be in the expected trimeric form. The COBRA2 HA was structurally similar to the naturally occurring H5 HA antigens and suggests the protein folds similar to known HA structures. Overall, our data allow us to formulate a hypothesis on the mechanism of increased breadth due to vaccination with the COBRA2 HA antigen, which is that the protein incorporates antigenic sites from numerous HA antigens, and elicits mAbs with limited breadth, but with diversity in targeted antigenic sites.

Indexed as

AnimalsAntibodies, MonoclonalAntibodies, ViralAntigens, ViralComputational BiologyCrystallography, X-RayHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A Virus, H5N1 SubtypeInfluenza, HumanInfluenza VaccinesMiceProtein ConformationProtein FoldingVaccinationAntibodies, MonoclonalAntibodies, ViralAntigens, Viralhemagglutinin, avian influenza A virusHemagglutinin Glycoproteins, Influenza VirusInfluenza VaccinesAntibodyHemagglutininInfluenzaVaccine

Identifiers

PMID31481254
PMCPMC6736729
OpenAlexW2970467221

What OpenQuestion holds

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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.