Evidence map›Paper›PMID 32267676›Full record

ArticleACS infectious diseases2020

Structure-Guided Molecular Grafting of a Complex Broadly Neutralizing Viral Epitope.

Goran Bajic, Max J Maron, Timothy M Caradonna, Ming Tian, Adam Mermelstein, Daniela Fera, Garnett Kelsoe, Masayuki Kuraoka, Aaron G Schmidt

Open access · greenAbstract read
In one paragraph

Article in ACS infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

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  13. Toward rational vaccine engineering.Advanced drug delivery reviews · 2022
    Review
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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

9 authors at 5 institutions in 1 country.

Goran BajicLaboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.ORCID 0000-0003-0480-4324
Max J MaronRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, United States.
Timothy M CaradonnaLaboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
Ming TianProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
Adam MermelsteinDepartment of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania 19081, United States.
Daniela FeraDepartment of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania 19081, United States.
Garnett KelsoeDuke Human Vaccine Institute, Duke University, Durham, North Carolina 27710, United States.
Masayuki KuraokaDepartment of Immunology, Duke University, Durham, North Carolina 27710, United States.
Aaron G SchmidtRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, United States.
Boston Children's Hospital · USDuke University · USSwarthmore College · USHarvard University · USRagon Institute of MGH, MIT and Harvard · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Virology CoreP01AI089618 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Jiwon Lee · 2011 to 2026
$40.0M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
Structures and Interactions of Antibodies Produced by Affinity MaturationU19AI117892 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HARRISON, STEPHEN COPLAN · 2015 to 2019
$9.2M
Epitope focusing to the receptor binding motif for a universal coronavirus vaccineR01AI146779 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SCHMIDT, AARON GREGORY · 2019 to 2023
$4.2M
NCI NIH HHS P30 CA006516NIAID NIH HHS P01 AI089618NIAID NIH HHS R01 AI146779NIAID NIH HHS U19 AI117892NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313
6 · The paper itself

Abstract

Antigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a "universal" influenza vaccine may come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use noncirculating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These "resurfaced" HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals. Through structure-guided optimization, we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and H1/H3 cross-reactive bnAbs with high affinity. Subsequent serological and single germinal center B cell analyses from murine prime-boost immunizations show that the rsHAs are both immunogenic and can augment the quality of elicited RBS-directed antibodies. Our structure-guided, RBS grafting approach provides candidate immunogens for selectively presenting a conserved viral epitope.

Indexed as

Antigen PresentationHemagglutinin Glycoproteins, Influenza VirusInfluenza VaccinesAnimalsAntibodies, NeutralizingAntibodies, ViralEpitopesHumansMiceAntibodies, NeutralizingAntibodies, ViralEpitopesHemagglutinin Glycoproteins, Influenza VirusInfluenza Vaccinesbroadly neutralizing antibodiesimmunogen designinfluenza hemagglutininprotein engineering

Identifiers

PMID32267676
PMCPMC7291361
OpenAlexW3014635301

What OpenQuestion holds

Textmetadata
LicenceTDM
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.