一种定量正痘病毒免疫测定法的开发与验证，用于评估和区分对猴痘感染和疫苗接种的血清学反应。

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

作者信息

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

机构信息

Centre for Experimental Pathogen Host Research (CEPHR), University College Dublin, Belfield, Dublin 4, Ireland; Department of Infectious Diseases, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.

Centre for Experimental Pathogen Host Research (CEPHR), University College Dublin, Belfield, Dublin 4, Ireland.

出版信息

EBioMedicine. 2025 Mar;113:105622. doi: 10.1016/j.ebiom.2025.105622. Epub 2025 Feb 22.

DOI:10.1016/j.ebiom.2025.105622

PMID:39987746

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11904509/

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.

摘要

背景

由猴痘病毒（MPXV）引起的猴痘疫情凸显了对评估猴痘免疫力的血清学检测的需求。改良安卡拉痘苗（MVA）疫苗，一种减毒痘苗病毒（VACV），已被批准用于预防猴痘。我们旨在开发一种定量免疫测定法，以区分感染和疫苗接种诱导的免疫力，并探索对猴痘感染和疫苗接种的血清学反应。

方法

在一项队列研究中，我们评估了一种针对来自有过猴痘、接种MVA疫苗或历史对照的成年人血浆中针对10种MPXV和3种VACV抗原的IgG的电化学发光测定法。使用ROC曲线确定区分i）血清阳性与未感染和ii）感染与疫苗接种诱导的血清阳性的敏感性和特异性。用广义相加模型分析抗体动力学。

结果

13种IgG抗体中的8种在各组之间显示出显著的滴度差异，确定了三种关键抗原：MPXVB6R、MPXVA27L和VACVB5。VACVB5 IgG滴度为0.082 IgG标准化单位（nu）时，对先前抗原暴露（感染或疫苗接种）的敏感性为74%（95%CI：59-82%），特异性为81%（73-96%）。仅对于感染，MPXVB6R IgG滴度为0.075 IgGnu时，敏感性为89%（82-98%），特异性为94%（86-100%）。为了区分感染与疫苗接种诱导的血清阳性，MPXVA27L IgG与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。VACVB5 IgG滴度随时间下降，猴痘后滴度高于疫苗接种后（p<0.0001）。