Evidence map›Paper›PMID 40778847›Full record

ArticleMicrobiology spectrum2025

Serological differentiation between naturally acquired mpox and MVA-BN-vaccine induced antibody responses using ratios of MPXV and VACV antigen pairs in the MSD immunoassay.

Aleksandra Pettke, Marton Keszei, Wanda Christ, Nuria Mayola Danés, Sara Gredmark-Russ, Sandra Söderholm, Finn Filén, Elisabet Storgärd, Victor Westergren, Victor Yman and 5 more

Abstract readEvaluation Study
In one paragraph

Article in Microbiology spectrum, 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. Article
  3. Review
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

15 authors.

Aleksandra Pettke *Public Health Agency of Sweden, Solna, Sweden.ORCID 0000-0001-9375-7755
Marton Keszei *Public Health Agency of Sweden, Solna, Sweden.
Wanda ChristDepartment of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
Nuria Mayola DanésDepartment of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
Sara Gredmark-RussDepartment of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
Sandra SöderholmPublic Health Agency of Sweden, Solna, Sweden.
Finn FilénDepartment of Infectious Diseases/Venhälsan Södersjukhuset, Stockholm, Sweden.
Elisabet StorgärdDepartment of Infectious Diseases/Venhälsan Södersjukhuset, Stockholm, Sweden.
Victor WestergrenDepartment of Infectious Diseases/Venhälsan Södersjukhuset, Stockholm, Sweden.
Victor YmanDepartment of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Johan AarumPublic Health Agency of Sweden, Solna, Sweden.
Jonas KlingströmPublic Health Agency of Sweden, Solna, Sweden.
Kari JohansenPublic Health Agency of Sweden, Solna, Sweden.
Anna Mia EkströmDepartment of Infectious Diseases/Venhälsan Södersjukhuset, Stockholm, Sweden.
Klara SondénPublic Health Agency of Sweden, Solna, Sweden.ORCID 0000-0003-1585-8475

Funding

Svenska Sällskapet för Medicinsk Forskning PG-22-0346Swedish Medical Society SLS-986999
6 · The paper itself

Abstract

This study's aim was to evaluate and benchmark the gold-standard methods neutralization test (NT) and immunofluorescence (IF), against a model linked to a multiplex immunoassay method for analysis of the highly cross-reactive serological responses against the monkeypox (MPXV)- and vaccinia (VACV) viruses. Serum samples from men who have sex with men were analyzed (22 with previous PCR-confirmed mpox episode, 53 MVA-BN-vaccinated, 61 unexposed to infection/vaccination). In-house NTs and IF established titers of mpox- and vaccinia-specific neutralizing and binding IgG antibodies, respectively. The commercial Orthopoxvirus Panel 1 multiplex immunoassay (Meso Scale Discovery [MSD]) was used to measure IgG against five homologous MPXV and VACV antigens. Antibody titers were studied in relation to infection and vaccination. The gold-standard NT and IF assays had ≥90% sensitivity identifying mpox-infected individuals. Despite high specificities in the unexposed group (≥91.8%), serum samples of vaccinated individuals strongly cross-reacted in the gold-standard assays with specificities of 73.6% (MPXV NT) and 43.4% (MPXV IF). Similarly, in the MSD assay, no individual antigen could differentiate between MPXV- or VACV-specific IgG antibodies. However, using ratios of IgG concentrations against three MPXV/VACV antigens enabled classification of separated mpox infected, vaccinated, and unexposed individuals with 88.9% accuracy. Through an innovative analytic approach, utilizing antibody response ratios to homologous MPXV and VACV antigen pairs, we demonstrate a model which differentiates MPXV-infected individuals from vaccinated and unexposed. This approach shows promise as a tool for transmission surveillance and outbreak monitoring, particularly in resource poor settings with low diagnostic capacity, and to prioritize vaccine. IMPORTANCE: Our study provides a uniquely broad perspective on orthopox serology by contrasting the gold standard NT and IF methods with the novel MSD multiplex assay and by providing an analysis model of multiplex data to separate previously mpox-infected, MVA-BN-vaccinated, and unexposed individuals.

Indexed as

Antibodies, ViralAntigens, ViralMonkeypox virusMpox, MonkeypoxVaccinia virusAdultAntibodies, NeutralizingCross ReactionsHumansImmunoassayImmunoglobulin GMaleNeutralization TestsSensitivity and SpecificityYoung AdultAntibodies, NeutralizingAntibodies, ViralAntigens, ViralImmunoglobulin GdifferentiationimmunizationMPXVserologyVACV

Identifiers

PMID40778847
PMCPMC12403559

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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.