Jones Scott, Hicks Bethany, Callaby Helen, Bailey Daniel, Gordon N Claire, Rampling Tommy, Houlihan Catherine, Jones Rachael, Pond Marcus, Mehta Ravi, Wright Deborah, Oeser Clarissa, Tonge Simon, Linley Ezra, Rowe Cathy, Hallis Bassam, Otter Ashley
Emerging Pathogen Serology Group, Vaccine Development Evaluation and Preparedness Centre, UK Health Security Agency, Wiltshire, UK.
Emerging Pathogen Serology Group, Vaccine Development Evaluation and Preparedness Centre, UK Health Security Agency, Wiltshire, UK.
Lancet Microbe. 2025 Apr;6(4):100987. doi: 10.1016/j.lanmic.2024.100987. Epub 2025 Jan 17.
In May, 2022, the first global outbreak of mpox (formerly known as monkeypox) occurred. In response, public health agencies in the UK have made smallpox vaccines available to individuals at the highest risk of infection. With mpox cases still being detected globally, novel tools are required to aid with diagnosis, serosurveillance, and the evaluation of immune responses following infection and immunisation with current and new vaccine candidates. Here, we describe the development of a multiplexed immunoassay, MpoxPlex, able to measure IgG responses to 12 Orthopoxvirus antigens concurrently and distinguish between responses to infection and vaccination.
Using the Luminex (DiaSorin, Saluggia, Italy) platform, antibody responses to vaccinia virus (VACV) antigens B5, A27, and A33 and monkeypox virus (MPXV) antigens E8, B6, B2, M1, A27, A35, H3, A29, and A5 were assessed in serum from individuals after MPXV infection (n=24) and after vaccination (n=75) with modified VACV Ankara-Bavarian Nordic. Assay characteristics and cutoffs were calculated by fitting receiver operating characteristic curves to the median fluorescence intensities of these positive samples and negative samples that were run alongside (n=435). P values were calculated using non-parametric Mann-Whitney, Kruskal-Wallis, and Dunn's multiple comparisons tests.
Using the results from a combination of eight antigens, we were able to distinguish samples as either post-vaccination or post-infection from negative samples with a sensitivity of 98% and a specificity of 95%. IgG responses to MPXV antigen A27 were able to distinguish post-MPXV infection with a sensitivity of 88% and a specificity of 97%. VACV antigen A27 and MPXV antigens A29 and A5 provided little diagnostic advantage.
With additional benefits over current serological assays, we believe this assay will provide substantial insight into the current global outbreak of mpox. MpoxPlex shows use for both serosurveillance and immunological studies of vaccination and infection.
Grant-in-aid funding to the Emerging Pathogen Serology Group at Porton Down, UK Health Security Agency.
2022年5月，首次出现了猴痘（以前称为猴痘）全球疫情。作为应对措施，英国公共卫生机构已向感染风险最高的个人提供天花疫苗。鉴于全球仍在检测到猴痘病例，需要新的工具来辅助诊断、血清学监测以及评估感染后和接种现有及新候选疫苗后的免疫反应。在此，我们描述了一种多重免疫测定法——猴痘病毒多重免疫测定法（MpoxPlex）的开发，该方法能够同时测量对12种正痘病毒抗原的IgG反应，并区分感染和疫苗接种后的反应。
使用Luminex（DiaSorin，意大利萨卢贾）平台，评估了猴痘病毒（MPXV）感染后（n = 24）和接种改良安卡拉痘苗病毒 - 巴伐利亚北欧公司疫苗后（n = 75）的个体血清中对痘苗病毒（VACV）抗原B5、A27和A33以及猴痘病毒抗原E8、B6、B2、M1、A27、A35、H3、A29和A5的抗体反应。通过将受试者工作特征曲线拟合到同时运行的这些阳性样本和阴性样本（n = 435）的中位荧光强度来计算测定特征和临界值。P值使用非参数曼 - 惠特尼检验、克鲁斯卡尔 - 沃利斯检验和邓恩多重比较检验进行计算。
使用八种抗原组合的结果，我们能够以98%的灵敏度和95%的特异性将接种疫苗后或感染后的样本与阴性样本区分开来。对猴痘病毒抗原A27的IgG反应能够以88%的灵敏度和97%的特异性区分猴痘病毒感染后样本。痘苗病毒抗原A27以及猴痘病毒抗原A29和A5的诊断优势不大。
与目前的血清学检测相比具有额外优势，我们相信该检测将为当前全球猴痘疫情提供重要见解。猴痘病毒多重免疫测定法显示可用于血清学监测以及疫苗接种和感染的免疫学研究。
英国卫生安全局波顿唐新兴病原体血清学小组的资助资金。
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