Arman Benediktus Yohan, Clarke Rebecca, Bharucha Tehmina, Fernandez Laura Gomez, Walsby-Tickle John, Deats Michael, Mosca Sara, Lin Qianqi, Banerjee Sneha, Chunekar Shrikrishna R, Patil Kundan D, Gairola Sunil, Dunachie Susanna, Merchant Hamid A, Stokes Robert, Kuwana Rutendo, Maes Alexandrine, Charrier Jean-Philippe, Probert Fay, Caillet Céline, Matousek Pavel, McCullagh James, Newton Paul N, Zitzmann Nicole, Gangadharan Bevin
Department of Biochemistry, University of Oxford, OX1 3QU, Oxford, UK.
Kavli Institute for Nanoscience Discovery, University of Oxford, OX1 3QU, Oxford, UK.
NPJ Vaccines. 2025 Jan 30;10(1):19. doi: 10.1038/s41541-024-01051-3.
The rapid development and worldwide distribution of COVID-19 vaccines is a remarkable achievement of biomedical research and logistical implementation. However, these developments are associated with the risk of a surge of substandard and falsified (SF) vaccines, as illustrated by the 184 incidents with SF and diverted COVID-19 vaccines which have been reported during the pandemic in 48 countries, with a paucity of methods for their detection in supply chains. In this context, matrix-assisted laser desorption ionisation-time of flight (MALDI-ToF) mass spectrometry (MS) is globally available for fast and accurate analysis of bacteria in patient samples, offering a potentially accessible solution to identify SF vaccines. We analysed the COVISHIELD™ COVID-19 vaccine; falsified versions of which were found in India, Myanmar and Uganda. We demonstrate for the first time that analysis of spectra from the vaccine vial label and its adhesive could be used as a novel approach to detect falsified vaccines. Vials tested by this approach could be retained in the supply chain since it is non-invasive. We also assessed whether MALDI-ToF MS could be used to distinguish the COVISHIELD™ vaccine from surrogates of falsified vaccines and the effect of temperature on vaccine stability. Both polysorbate 80 and L-histidine excipients of the genuine vaccine could be detected by the presence of a unique combination of MALDI-ToF MS peaks which allowed us to distinguish between the genuine vaccines and falsified vaccine surrogates. Furthermore, even if a falsified product contained polysorbate 80 at the same concentration as used in the genuine vaccine, the characteristic spectral profile of polysorbate 80 used in genuine products is a reliable internal marker for vaccine authenticity. Our findings demonstrate that MALDI-ToF MS analysis of extracts from vial labels and the vaccine excipients themselves can be used independently to detect falsified vaccines. This approach has the potential to be integrated into the national regulatory standards and WHO's Prevent, Detect, and Respond strategy as a novel effective tool for detecting falsified vaccines.
新冠疫苗的迅速研发和全球分发是生物医学研究与后勤实施方面的一项卓越成就。然而，这些进展伴随着不合格和伪造（SF）疫苗激增的风险，正如在大流行期间48个国家报告的184起SF和挪用新冠疫苗事件所表明的那样，供应链中缺乏检测这些疫苗的方法。在这种背景下，基质辅助激光解吸电离飞行时间（MALDI-ToF）质谱（MS）在全球范围内可用于快速准确地分析患者样本中的细菌，为识别SF疫苗提供了一种潜在可行的解决方案。我们分析了COVISHIELD™新冠疫苗；在印度、缅甸和乌干达发现了该疫苗的伪造版本。我们首次证明，对疫苗瓶标签及其粘合剂的光谱分析可作为检测伪造疫苗的一种新方法。通过这种方法检测的小瓶可以保留在供应链中，因为它是非侵入性的。我们还评估了MALDI-ToF MS是否可用于区分COVISHIELD™疫苗与伪造疫苗的替代品，以及温度对疫苗稳定性的影响。通过MALDI-ToF MS峰的独特组合可以检测到正品疫苗的聚山梨醇酯80和L-组氨酸辅料，这使我们能够区分正品疫苗和伪造疫苗的替代品。此外，即使伪造产品中聚山梨醇酯80的浓度与正品疫苗相同，正品产品中使用的聚山梨醇酯80的特征光谱图也是疫苗真实性的可靠内部标记。我们的研究结果表明，对小瓶标签提取物和疫苗辅料本身进行MALDI-ToF MS分析可独立用于检测伪造疫苗。这种方法有可能作为一种检测伪造疫苗的新型有效工具，被纳入国家监管标准和世卫组织的“预防、检测和应对”战略。
