Evidence map›Paper›PMID 30642961›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Multistate design of influenza antibodies improves affinity and breadth against seasonal viruses.

Alexander M Sevy, Nicholas C Wu, Iuliia M Gilchuk, Erica H Parrish, Sebastian Burger, Dina Yousif, Marcus B M Nagel, Kevin L Schey, Ian A Wilson, James E Crowe and 1 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Design and discovery of metamorphic proteins.Current opinion in structural biology · 2022
    Review
  11. Review
  12. Review
  13. Article
  14. Predicting susceptibility to SARS-CoV-2 infection based on structural differences in ACE2 across species.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  15. Article
  16. Review
  17. Computer-based Engineering of Thermostabilized Antibody Fragments.AIChE journal. American Institute of Chemical Engineers · 2020
    Article
  18. Article
  19. Article
  20. Review
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

11 authors.

Alexander M SevyChemical & Physical Biology Program, Vanderbilt University, Nashville, TN 37235.ORCID 0000-0002-2380-2861
Nicholas C WuDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
Iuliia M GilchukVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232.
Erica H ParrishVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232.
Sebastian BurgerDepartment of Mathematics, University of Leipzig, 04109 Leipzig, Germany.
Dina YousifVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232.
Marcus B M NagelCenter for Structural Biology, Vanderbilt University, Nashville, TN 37235.
Kevin L ScheyVanderbilt Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
James E CroweChemical & Physical Biology Program, Vanderbilt University, Nashville, TN 37235; james.crowe@vanderbilt.edu jens.meiler@vanderbilt.edu.ORCID 0000-0002-0049-1079
Jens MeilerChemical & Physical Biology Program, Vanderbilt University, Nashville, TN 37235; james.crowe@vanderbilt.edu jens.meiler@vanderbilt.edu.

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Structure based design of antibodies and vaccinesU19AI117905 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SCHIEF, WILLIAM R. · 2015 to 2019
$12.0M
High-Performance Computer Cluster for Biomedical ResearchS10OD023680 · OD · VANDERBILT UNIVERSITY · PI MEILER, JENS · 2017 to 2017
$587k
NIAID NIH HHS U19 AI117905NIH HHS S10 OD023680
6 · The paper itself

Abstract

Influenza is a yearly threat to global public health. Rapid changes in influenza surface proteins resulting from antigenic drift and shift events make it difficult to readily identify antibodies with broadly neutralizing activity against different influenza subtypes with high frequency, specifically antibodies targeting the receptor binding domain (RBD) on influenza HA protein. We developed an optimized computational design method that is able to optimize an antibody for recognition of large panels of antigens. To demonstrate the utility of this multistate design method, we used it to redesign an antiinfluenza antibody against a large panel of more than 500 seasonal HA antigens of the H1 subtype. As a proof of concept, we tested this method on a variety of known antiinfluenza antibodies and identified those that could be improved computationally. We generated redesigned variants of antibody C05 to the HA RBD and experimentally characterized variants that exhibited improved breadth and affinity against our panel. C05 mutants exhibited improved affinity for three of the subtypes used in design by stabilizing the CDRH3 loop and creating favorable electrostatic interactions with the antigen. These mutants possess increased breadth and affinity of binding while maintaining high-affinity binding to existing targets, surpassing a major limitation up to this point.

Indexed as

Amino Acid SequenceAntibodies, NeutralizingAntibodies, ViralCrystallography, X-RayHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A virusInfluenza, HumanSeasonsAntibodies, NeutralizingAntibodies, ViralHemagglutinin Glycoproteins, Influenza Virusantibody designbroadly neutralizing antibodiesinfluenzamultistate design

Identifiers

PMID30642961
PMCPMC6358683

What OpenQuestion holds

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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.