Evidence map›Paper›PMID 21917960›Full record

ArticleJournal of virology2011

Poorly neutralizing cross-reactive antibodies against the fusion loop of West Nile virus envelope protein protect in vivo via Fcgamma receptor and complement-dependent effector mechanisms.

Matthew R Vogt, Kimberly A Dowd, Michael Engle, Robert B Tesh, Syd Johnson, Theodore C Pierson, Michael S Diamond

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
10.7field-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

90 citing papers in PubMed, 129 citations in OpenAlex.

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  18. Immunoglobulin G subclasses confer protection againstProceedings of the National Academy of Sciences of the United States of America · 2023
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  20. Review

30 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

7 authors at 5 institutions in 1 country.

Matthew R VogtDepartment of Pathology & Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St. Louis, MO 63110, USA.
Kimberly A Dowd
Michael Engle
Robert B Tesh
Syd Johnson
Theodore C Pierson
Michael S Diamond
Washington University in St. Louis · USMacroGenics (United States) · USNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USThe University of Texas Medical Branch at Galveston · US

Funding

Virology and Smallpox VaccinationsU54AI057160 · NIAID · WASHINGTON UNIVERSITY · PI RAY, RANJIT · 2003 to 2013
$80.9M
Monoclonal Antibody Therapy for West Nile VirusU01AI061373 · NIAID · WASHINGTON UNIVERSITY · PI DIAMOND, MICHAEL S · 2005 to 2009
$5.1M
Safe Antibody Prophylaxis and Therapy Against Dengue VirusU01AI077955 · NIAID · WASHINGTON UNIVERSITY · PI DIAMOND, MICHAEL S · 2008 to 2011
$3.4M
Analysis of the neutralizing antibody response following flavivirus infectionZIAAI001022 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI PIERSON, THEODORE · 2009 to 2016
$1.7M
Intramural NIH HHSNIAID NIH HHS R01-AI077955NIAID NIH HHS U01 AI061373NIAID NIH HHS U01 AI077955NIAID NIH HHS U54 AI057160PHS HHS 27200004PHS HHS 272201D000401
6 · The paper itself

Abstract

The human antibody response to flavivirus infection is dominantly directed against a cross-reactive epitope on the fusion loop of domain II (DII-FL) of the envelope (E) protein. Although antibodies against this epitope fail to recognize fully mature West Nile virus (WNV) virions and accordingly neutralize infection poorly in vitro, their functional properties in vivo remain less well understood. Here, we show that while passive transfer of poorly neutralizing monoclonal antibodies (MAb) and polyclonal antibodies against the DII-FL epitope protect against lethal WNV infection in wild-type mice, they fail to protect mice lacking activating Fcγ receptors (FcγR) and the complement opsonin C1q. Consistent with this, an aglycosyl chimeric mouse-human DII-FL MAb (E28) variant that lacks the ability to engage FcγR and C1q also did not protect against WNV infection in wild-type mice. Using a series of immunodeficient mice and antibody depletions of individual immune cell populations, we demonstrate that the nonneutralizing DII-FL MAb E28 does not require T, B, or NK cells, inflammatory monocytes, or neutrophils for protection. Rather, E28 treatment decreased viral load in the serum early in the course of infection, which resulted in blunted dissemination to the brain, an effect that required phagocytic cells, C1q, and FcγRIII (CD16). Overall, these studies enhance our understanding of the functional significance of immunodominant, poorly neutralizing antibodies in the polyclonal human anti-flavivirus response and highlight the limitations of current in vitro surrogate markers of protection, such as cell-based neutralization assays, which cannot account for the beneficial effects conferred by these antibodies.

Indexed as

Cross ReactionsAnimalsAntibodies, NeutralizingAntibodies, ViralComplement System ProteinsDisease Models, AnimalImmunization, PassiveMiceMice, Inbred C57BLPhagocytosisReceptors, IgGRodent DiseasesSurvival AnalysisViral Envelope ProteinsWest Nile virusAntibodies, NeutralizingAntibodies, ViralComplement System ProteinsReceptors, IgGViral Envelope Proteins

Identifiers

PMID21917960
PMCPMC3209272
OpenAlexW2128358667

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.