Development and validation of a quantitative Orthopoxvirus immunoassay to evaluate and differentiate serological responses to Mpox infection and vaccination.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2025-03-01 Epub Date: 2025-02-22 DOI:10.1016/j.ebiom.2025.105622

Joanne Byrne, Gurvin Saini, Alejandro Garcia-Leon, Dana Alalwan, Peter Doran, Alan Landay, Liem Binh Luong Nguyen, Cathal O'Broin, Stefano Savinelli, Jane A O'Halloran, Aoife Cotter, Mary Horgan, Christine Kelly, Corinna Sadlier, Eoghan de Barra, Virginie Gautier, Patrick W G Mallon, Eoin R Feeney

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Abstract

Background: The Mpox outbreak, caused by Monkeypox virus (MPXV), underscores the need for a serological assay to assess Mpox immunity. Modified Vaccinia Ankara (MVA) vaccine, an attenuated vaccinia virus (VACV), is authorised for Mpox prevention. We aimed to develop a quantitative immunoassay to differentiate infection- and vaccination-induced immunity and explore serological responses to Mpox infection and vaccination.

Methods: We evaluated an electrochemiluminescence assay targeting IgG to 10 MPXV and 3 VACV antigens in plasma from adults in a cohort study with previous Mpox, MVA-vaccination, or historical controls. Sensitivity and specificity to distinguish i) seropositive versus naive and ii) infection- versus vaccination-induced seropositivity were determined using ROC curves. Antibody kinetics were analysed with generalised additive models.

Findings: Eight of the thirteen IgG antibodies showed significant titre differences across groups identifying three key antigens: MPXVB6R, MPXVA27L, and VACVB5. A VACVB5 IgG titre of 0.082 IgG normalised units (nu) offered 74% (95% CI: 59-82%) sensitivity and 81% (73-96%) specificity for previous antigen exposure (infection or vaccine). For infection alone, an MPXVB6R IgG titre of 0.075 IgGnu provided 89% (82-98%) sensitivity and 94% (86-100%) specificity. To differentiate infection from vaccination-induced seropositivity, the sum of MPXVA27L IgG and the B6R/VACVB5 ratio provided 89% (80-96%) sensitivity and 80% (74-84%) specificity. VACVB5 IgG titres declined over time, with higher titres post-Mpox than post-vaccination (p < 0.0001).

Interpretation: This assay demonstrates high sensitivity and specificity in quantifying and differentiating between antibody responses to Mpox infection and vaccination. Post-Mpox antibody responses were higher than post-vaccination, though both waned over time.

Funding: Health Research Board (MONKEYVAX-2022-1), University College Dublin School of Medicine.

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开发和验证定量正痘病毒免疫测定，以评估和区分对m痘感染和疫苗接种的血清学反应。

背景：由猴痘病毒（MPXV）引起的m痘暴发强调了对评估m痘免疫的血清学检测的必要性。改良安卡拉牛痘（MVA）疫苗是一种减毒牛痘病毒（VACV），已被批准用于预防m痘。我们的目的是建立一种定量免疫分析来区分感染和疫苗诱导的免疫，并探索对m痘感染和疫苗接种的血清学反应。方法：我们在一项队列研究中评估了针对成人血浆中10种MPXV和3种VACV抗原的IgG的电化学发光试验，这些成人血浆中有既往的m痘、mva疫苗接种或历史对照。使用ROC曲线确定区分i)血清阳性与幼稚和ii)感染与疫苗诱导血清阳性的敏感性和特异性。用广义加性模型分析抗体动力学。结果：13种IgG抗体中有8种在三种关键抗原（MPXVB6R、MPXVA27L和VACVB5）上显示显著滴度差异。VACVB5 IgG滴度为0.082 IgG标准化单位（nu），对既往抗原暴露（感染或疫苗）的敏感性为74% (95% CI: 59-82%)，特异性为81%（73-96%）。对于单独感染，MPXVB6R IgG滴度为0.075 IgGnu提供89%（82-98%）的敏感性和94%（86-100%）的特异性。为了区分感染和疫苗诱导的血清阳性，MPXVA27L IgG和B6R/VACVB5比值的总和提供了89%（80-96%）的敏感性和80%（74-84%）的特异性。随着时间的推移，VACVB5 IgG的滴度下降，m痘后的滴度高于疫苗接种后的滴度(p)解释：该试验在定量和区分m痘感染和疫苗接种的抗体反应方面显示出高灵敏度和特异性。m痘后抗体反应高于接种疫苗后，尽管两者都随着时间的推移而减弱。资助：卫生研究委员会（MONKEYVAX-2022-1），都柏林大学医学院。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.