Evidence map›Paper›PMID 24778221›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution.

Xian-Chun Tang, Sudhakar S Agnihothram, Yongjun Jiao, Jeremy Stanhope, Rachel L Graham, Eric C Peterson, Yuval Avnir, Aimee St Clair Tallarico, Jared Sheehan, Quan Zhu and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed, 1 pooled it
16.2field-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.

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

180 citing papers in PubMed, 1 synthesis or guideline pooled it, 246 citations in OpenAlex.

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120 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 1 country.

Xian-Chun TangDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
Sudhakar S AgnihothramDepartments of Microbiology and Immunology and.
Yongjun JiaoDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
Jeremy StanhopeDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
Rachel L GrahamDepartments of Microbiology and Immunology and.
Eric C PetersonDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
Yuval AvnirDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
Aimee St Clair TallaricoDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
Jared SheehanDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
Quan ZhuDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
Ralph S BaricDepartments of Microbiology and Immunology andEpidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 rbaric@ad.unc.edu wayne_marasco@dfci.harvard.edu.
Wayne A MarascoDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and rbaric@ad.unc.edu wayne_marasco@dfci.harvard.edu.
Harvard University · USDana-Farber Cancer Institute · USUniversity of North Carolina at Chapel Hill · US

Funding

Broad Spectrum Neutralizing Human Abs to SARS and Related CoronavirusesR01AI085524 · NIAID · DANA-FARBER CANCER INST · PI MARASCO, WAYNE A. · 2010 to 2014
$5.4M
NIAID NIH HHS R01 AI085524NIAID NIH HHS R01AI085524
6 · The paper itself

Abstract

The newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a Severe Acute Respiratory Syndrome-like disease with ∼43% mortality. Given the recent detection of virus in dromedary camels, zoonotic transfer of MERS-CoV to humans is suspected. In addition, little is known about the role of human neutralizing Ab (nAb) pressure as a driving force in MERS-CoV adaptive evolution. Here, we used a well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein. These nAbs bind to three different epitopes in the RBD and human dipeptidyl peptidase 4 (hDPP4) interface with subnanomolar/nanomolar binding affinities and block the binding of MERS-CoV Spike protein with its hDPP4 receptor. Escape mutant assays identified five amino acid residues that are critical for neutralization escape. Despite the close proximity of the three epitopes on the RBD interface, escape from one epitope did not have a major impact on neutralization with Abs directed to a different epitope. Importantly, the majority of escape mutations had negative impacts on hDPP4 receptor binding and viral fitness. To our knowledge, these results provide the first report on human nAbs against MERS-CoV that may contribute to MERS-CoV clearance and evolution. Moreover, in the absence of a licensed vaccine or antiviral for MERS, this panel of nAbs offers the possibility of developing human mAb-based immunotherapy, especially for health-care workers.

Indexed as

Amino Acid SequenceAnimalsAntibodies, NeutralizingAntibodies, ViralAntiviral AgentsBiological EvolutionCommunicable Diseases, EmergingCoronavirusCoronavirus InfectionsDipeptidyl Peptidase 4HEK293 CellsHumansImmunoglobulin GMolecular Sequence DataPhylogenySpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralAntiviral AgentsDipeptidyl Peptidase 4DPP4 protein, humanImmunoglobulin GSpike Glycoprotein, CoronavirusViral Vaccinesbiodefenseemerging pathogenhumoral immunityIGHV1–69zoonosis

Identifiers

PMID24778221
PMCPMC4024880
OpenAlexW2170239105

What OpenQuestion holds

Textmetadata
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.