Evidence map›Paper›PMID 28750738›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Dengue Virus Evades AAV-Mediated Neutralizing Antibody Prophylaxis in Rhesus Monkeys.

Diogo M Magnani, Michael J Ricciardi, Varian K Bailey, Martin J Gutman, Núria Pedreño-Lopez, Cassia G T Silveira, Helen S Maxwell, Aline Domingues, Lucas Gonzalez-Nieto, Qin Su and 13 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.5field-weighted citation impact, top 27% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Mechanistic blockade ofAntimicrobial agents and chemotherapy · 2025
    Article
  2. Article
  3. Dengue: Update on Clinically Relevant Therapeutic Strategies and Vaccines.Current treatment options in infectious diseases · 2023
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
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

23 authors at 6 institutions in 2 countries.

Diogo M MagnaniDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Michael J RicciardiDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Varian K BaileyDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Martin J GutmanDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Núria Pedreño-LopezDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Cassia G T SilveiraDivision of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo 246903, Brazil.
Helen S MaxwellDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Aline DominguesDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Lucas Gonzalez-NietoDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Qin SuThe Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Ruchi M NewmanRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Melissa PackRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Mauricio A MartinsDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
José M Martinez-NavioDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Sebastian P FuchsDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Eva G RakaszWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA.
Todd M AllenRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Stephen S WhiteheadLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Dennis R BurtonRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Guangping GaoThe Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Ronald C DesrosiersDepartment of Pathology, University of Miami, Miami, FL 33136, USA.
Esper G KallasDivision of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo 246903, Brazil.
David I WatkinsDepartment of Pathology, University of Miami, Miami, FL 33136, USA. Electronic address: dwatkins@med.miami.edu.
University of Miami · USRagon Institute of MGH, MIT and Harvard · USUniversidade de São Paulo · BRUniversity of Massachusetts Chan Medical School · USNational Institutes of Health · USUniversity of Wisconsin–Madison · US

Funding

WNPRC Supplemental Request for Nonhuman Primate Enclosures to Equip HIV/AIDS-Related Research FacilitiesP51OD011106 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI Dorota A. Grejner-Brzezinska · 2012 to 2026
$150.7M
Laboratory And Preclinical Studies Of FlavivirusesZIAAI000891 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI WHITEHEAD, STEPHEN · 2009 to 2025
$17.5M
Yellow Fever Vector Development P01AI094420 · NIAID · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BONALDO, MYRNA C · 2012 to 2016
$11.4M
Immunoglobulins Delivered by AVV Vector for the Prevention of SIV InfectionR01AI098446 · NIAID · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI DESROSIERS, RONALD C · 2012 to 2021
$6.6M
Ipilimumab as an adjuvant for HIV vaccinesK01OD023032 · OD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI MARTINS, MAURICIO DE AGUIAR · 2016 to 2018
$993k
NIAID NIH HHS P01 AI094420NIAID NIH HHS R01 AI098446NIH HHS K01 OD023032NIH HHS P51 OD011106
6 · The paper itself

Abstract

Development of vaccines against mosquito-borne Flaviviruses is complicated by the occurrence of antibody-dependent enhancement (ADE), which can increase disease severity. Long-term delivery of neutralizing antibodies (nAbs) has the potential to effectively block infection and represents an alternative to vaccination. The risk of ADE may be avoided by using prophylactic nAbs harboring amino acid mutations L234A and L235A (LALA) in the immunoglobulin G (IgG) constant region. Here, we used recombinant adeno-associated viruses (rAAVs) to deliver the anti-dengue virus 3 (DENV3) nAb P3D05. While the administration of rAAV-P3D05-rhesus immunoglobulin G1 (rhIgG1)-LALA to rhesus macaques engendered DENV3-neutralizing activity in serum, it did not prevent infection. The emergence of viremia following DENV3 challenge was delayed by 3-6 days in the rAAV-treated group, and replicating virus contained the envelope mutation K64R. This neutralization-resistant variant was also confirmed by virus outgrowth experiments in vitro. By delivering P3D05 with unmutated Fc sequences, we further demonstrated that DENV3 also evaded wild-type nAb prophylaxis, and serum viral loads appeared to be higher in the presence of low levels of unmutated P3D05-rhIgG1. Our study shows that a vectored approach for long-term delivery of nAbs with the LALA mutations is promising, but prophylaxis using a single nAb is likely insufficient at preventing DENV infection and replication.

Indexed as

AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralDengue VirusDependovirusEnzyme-Linked Immunosorbent AssayFemaleMacaca mulattaMaleAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAAVdengue virusgene deliverymonoclonal antibodyneutralizing antibody

Identifiers

PMID28750738
PMCPMC5628771
OpenAlexW2727807549

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.