Wang Xiaoyan, Aurich Konstanze, Zhang Wenli, Ehrhardt Anja, Greinacher Andreas, Bayer Wibke
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
Institute for Transfusion Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
Viruses. 2024 Nov 7;16(11):1747. doi: 10.3390/v16111747.
Adenoviruses are important human pathogens that are widespread and mainly associated with respiratory and gastrointestinal infections. In a previous study on human adenovirus (HAdV) seroprevalence, we observed reduced binding antibody levels against a range of HAdV types in sera collected from students in 2021 compared to sera collected before the SARS-CoV-2 pandemic. In this follow-up study, we wanted to verify this observation in a cohort of regular blood donors for whom serial samples were available. Therefore, HAdV-specific binding antibody levels were analyzed in sera collected over a 5-year period from 2018 to 2022 in a cohort of 60 regular donors to the blood bank of the University Hospital in Greifswald, Germany. Using ELISA-based assays, we quantified the binding antibody responses against 39 HAdV types. On the cohort level, we found largely stable antibody levels over the analyzed time period, with the highest antibody responses against HAdV-C1, -D25, -D26, -E4, -D10, -D27, -C5, -D75, -C2, and -C6. Only minor but significant reductions in comparison to the first serum samples from 2018 were detected for antibody levels in 2021 and 2022 against the low-prevalent types HAdV-A31, -D8, -D20, -D37, -D65, and -D69. On the other hand, we detected fluctuations in antibody levels on the individual level, with strong increases in antibody levels indicative of novel antigen contact. Interestingly, we frequently found simultaneous changes in antibody responses against multiple HAdV types, resulting in strong correlations of antibody responses against distinct clusters of HAdVs suggesting extensive cross-reactivity of HAdV-specific antibodies. To our knowledge, this is the first study of antibodies against a broad range of HAdV types in serum samples collected from a cohort of individuals over a prolonged period, and our data provide important insight into the long-term stability of HAdV-specific antibody levels. In this cohort of regular blood donors, we did not observe any major impact of the SARS-CoV-2 pandemic on HAdV immunity. Correlations of changes in antibody levels against different types indicate cross-reactivity of HAdV-specific antibodies that are important to consider for HAdV vector development. Our data also reveal possible candidates for future development of HAdV-based vectors.
腺病毒是重要的人类病原体，广泛存在，主要与呼吸道和胃肠道感染相关。在先前一项关于人类腺病毒（HAdV）血清流行率的研究中，我们观察到，与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行之前采集的血清相比，2021年从学生中采集的血清中针对一系列HAdV类型的结合抗体水平有所降低。在这项后续研究中，我们想在一批有系列样本的定期献血者中验证这一观察结果。因此，对德国格赖夫斯瓦尔德大学医院血库的60名定期献血者在2018年至2022年的5年期间采集的血清中的HAdV特异性结合抗体水平进行了分析。我们使用基于酶联免疫吸附测定（ELISA）的检测方法，对针对39种HAdV类型的结合抗体反应进行了定量。在队列水平上，我们发现在分析的时间段内抗体水平基本稳定，对HAdV-C1、-D25、-D26、-E4、-D10、-D27、-C5、-D75、-C2和-C6的抗体反应最高。与2018年的首批血清样本相比，仅检测到2021年和2022年针对低流行类型HAdV-A31、-D8、-D20、-D37、-D65和-D69的抗体水平有轻微但显著的降低。另一方面，我们在个体水平上检测到抗体水平的波动，抗体水平的强烈升高表明有新的抗原接触。有趣的是，我们经常发现针对多种HAdV类型的抗体反应同时发生变化，导致针对不同HAdV簇的抗体反应之间有很强的相关性，这表明HAdV特异性抗体具有广泛的交叉反应性。据我们所知，这是第一项对从一批个体中长时间采集的血清样本中针对多种HAdV类型的抗体进行的研究，我们的数据为HAdV特异性抗体水平的长期稳定性提供了重要见解。在这批定期献血者中，我们没有观察到SARS-CoV-2大流行对HAdV免疫力有任何重大影响。针对不同类型的抗体水平变化之间的相关性表明HAdV特异性抗体具有交叉反应性，这在HAdV载体开发中是需要考虑的重要因素。我们的数据还揭示了基于HAdV的载体未来开发的可能候选对象。
