Evidence map›Paper›PMID 40753572›Full record

ArticleCell reports2025

Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine.

Ariadna Grinyo-Escuer, Srikar Reddy, Agnes L Chenine, J Charles Whitbeck, Sonya Jacobsen, Allison Sheetz, Kyle Doolan, Diana M Norden, Nolan Frey, Frederick W Holtsberg and 7 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

17 authors.

Ariadna Grinyo-EscuerIntegral Molecular, Inc., Philadelphia, PA, USA.
Srikar ReddyIntegral Molecular, Inc., Philadelphia, PA, USA.
Agnes L ChenineIBT Bioservices, Rockville, MD, USA.
J Charles WhitbeckIntegral Molecular, Inc., Philadelphia, PA, USA.
Sonya JacobsenIntegral Molecular, Inc., Philadelphia, PA, USA.
Allison SheetzIntegral Molecular, Inc., Philadelphia, PA, USA.
Kyle DoolanIntegral Molecular, Inc., Philadelphia, PA, USA.
Diana M NordenIntegral Molecular, Inc., Philadelphia, PA, USA.
Nolan FreyIntegral Molecular, Inc., Philadelphia, PA, USA.
Frederick W HoltsbergIBT Bioservices, Rockville, MD, USA.
M Javad AmanIBT Bioservices, Rockville, MD, USA.
Katja FinkSingapore Immunology Network (SIgN), Agency for Science Technology and Research (A(∗)STAR), Singapore, Singapore.
Michael S DiamondDepartments of Medicine, Molecular Microbiology, and Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
John S SchieffelinDepartment of Pediatrics, Section of Infectious Diseases, Tulane University School of Medicine, New Orleans, LA, USA.
James E CroweDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Edgar DavidsonIntegral Molecular, Inc., Philadelphia, PA, USA.
Benjamin J DoranzIntegral Molecular, Inc., Philadelphia, PA, USA. Electronic address: bdoranz@integralmolecular.com.

Funding

Antibody-based Protection against FlavivirsesR01AI073755 · NIAID · WASHINGTON UNIVERSITY · PI DIAMOND, MICHAEL S, FREMONT, DAVED H. · 2007 to 2022
$11.4M
B-Cell Epitope Discovery and Mechanisms of Antibody Protection for ZIKV, MARV, VEEV Envelope Proteins 75N93019C00073 · NIAID · INTEGRAL MOLECULAR · PI DORANZ, BENJAMIN · 2019 to 2023
$7.5M
ANTIBODY-BASED PROTECTION AGAINST FLAVIVIRUSESU01AI073755 · NIAID · WASHINGTON UNIVERSITY · PI James E Crowe, Michael S Diamond · 2024 to 2026
$3.3M
NIAID NIH HHS 75N93019C00073NIAID NIH HHS R01 AI073755NIAID NIH HHS U01 AI073755
6 · The paper itself

Abstract

The development of a Zika virus (ZIKV) vaccine is complicated by the high homology between ZIKV and dengue virus (DENV) envelope (E) proteins, resulting in immunological cross-reactivity that can exacerbate disease through antibody-dependent enhancement (ADE). Here, we screen 121 anti-DENV monoclonal antibodies (mAbs) for cross-reactivity with ZIKV E proteins. We identify 70 cross-reactive mAbs, 66 of which have epitopes that included at least one of seven E protein residues conserved among DENV1-DENV4 and ZIKV (R73, E79, W101, L107, F108, K110, and W212), establishing these residues as the key determinants of DENV-ZIKV cross-reactivity. Using these data, we engineer a ZIKV E protein variant with 10 mutations ("ZIKVm10") that reduces cross-reactivity with DENV mAbs in vitro and minimizes the induction of anti-DENV antibodies in immunized mice. Passive serum transfer from ZIKVm10-immunized mice confers near-complete protection against lethal ZIKV challenge and reduced ADE for DENV infection, providing a pathway for improved ZIKV vaccine design.

Indexed as

Dengue VirusViral VaccinesZika VirusZika Virus InfectionAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCross ReactionsDengueEpitopesFemaleHumansMiceMice, Inbred BALB CViral Envelope ProteinsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesViral Envelope ProteinsViral Vaccinesantibody enhancementantigen engineeringCP: ImmunologyCP: Microbiologyepitope mappingimmunogenic cross-reactivityvirus envelope

Identifiers

PMID40753572
PMCPMC12440574

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.