Evidence map›Paper›PMID 41282907›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Differentiating Mpox Infection and Vaccination Using a Validated Multiplex Orthopoxvirus IgG Serology Assay.

Jonathan C Reed, Cecilia Downs, Kaden McAllister, Clarice Mauer, Christopher L McClurkan, Donna Wilson, Kate Holzhauer, Jane A Dickerson, Chase A Cannon, Tara M Babu and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Jonathan C ReedDepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
Cecilia DownsDepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
Kaden McAllisterDepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
Clarice MauerDepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
Christopher L McClurkanDepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
Donna WilsonDepartment of Laboratories, Seattle Children's Hospital, Seattle, WA, USA.
Kate HolzhauerDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
Jane A DickersonDepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
Chase A CannonDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
Tara M BabuDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
Matthew R GoldenDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
David M KoelleDepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
Alexander L GreningerDepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.ORCID 0000-0002-7443-0527

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI CONNIE L CELUM · 1988 to 2026
$104.9M
NIAID NIH HHS P30 AI027757
6 · The paper itself

Abstract

The resurgence of monkeypox virus (MPXV) outbreaks has increased demand for validated serological assays to assess exposure and immunity. Cross-reactivity among orthopoxivuses, stemming from high sequence conservation, complicates distinguishing antibody responses from natural MPXV infection versus vaccination or other orthopoxvirus exposures. We validated the Meso Scale Discovery (MSD) V-PLEX Orthopoxvirus Panel 1 (IgG) Kit, which quantifies antibody levels to five MPXV antigens and their vaccina virus (VACV) orthologs, following Good Clinical Laboratory Practice (GCLP) guidelines. We assessed assay performance using serum from 26 individuals with prior mpox, 52 JYNNEOS vaccine recipients, and 179 unexposed controls. The assay reliably detected antibody responses in all exposed cohorts with peak levels observed 2-months post-vaccination. Antibody levels to specific antigens also correlated with Modified Vaccinia Ankara (MVA) neutralization titer, particularly for MPXV B6R/VACV B5R, MPXV E8L/VACV D8L, and MPXV M1R/VACV L1. Receiver operating characteristic (ROC) analysis showed that some individual antigens achieved high sensitivity and specificity for exposure detection (AUC > 0.96 for VACV D8L, MPXV B6R, VACV B5R); however, individual antigens performed poorly in distinguishing infection from vaccination. In contrast, antibody level ratios between some MPXV and VACV orthologs effectively differentiated MPXV infection from vaccinia vaccination with high sensitivity and specificity (e.g. MPXV A35R/VACV A33R ortholog ratio, AUC = 0.97, sensitivity = 0.97, specificity = 0.96). Our findings validate the MSD assay for clinical research and serosurveillance to assess MPXV immunity and support the utility of ortholog pair ratio analysis as a strategy to discriminate vaccinated and infected individuals.

Identifiers

PMID41282907
PMCPMC12636651

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.