Arman Benediktus Yohan, Magri Andrea, Barbaglia Matteo N, Petherbridge Lawrence, Brook Jennifer, Bharucha Tehmina, Legge Isabelle, Walsby-Tickle John, Deats Michael, Banerjee Sneha, Mosca Sara, Jena Rajender, Ranade Dnyanesh S, Chunekar Shrikrishna R, Patil Kundan D, Gairola Sunil, Merchant Hamid A, Stokes Robert, Kuwana Rutendo, Maes Alexandrine, James Tim, Green Catherine, McCullagh James, Matousek Pavel, Caillet Céline, 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.
Int J Pharm X. 2025 Dec 11;11:100467. doi: 10.1016/j.ijpx.2025.100467. eCollection 2026 Jun.
Maintaining cold-chain integrity is vital for vaccines to ensure that they remain within the recommended temperature limits during routine storage and transportation. This ensures vaccine stability, efficacy, and avoids degradation. Here, we propose rapid and low-cost tests based on simple glucose assays to detect heat-exposed degraded sucrose-containing vaccines through sucrose's inherent gradual conversion to glucose when exposed to elevated temperatures. Bioluminescent and colorimetric assays and a clinical biochemical analyser for urine samples could successfully determine effects of heat exposure on vaccines by detecting a significant increase in glucose levels. We show that this increase in glucose also correlates with the loss of vaccine potency. When vaccines were incubated at 37 and 45 °C, the bioluminescent assay was able to detect an increase in glucose levels from 12 h of heat exposure. The biochemical analyser could successfully detect increased glucose levels in a COVID-19 vaccine which had been exposed to 37 and 45 °C. Most importantly, the colorimetric assay has the advantage of producing a colour change visually upon simply mixing the vaccine with a reagent without the need for a plate reader or any other sophisticated devices. To our knowledge, this is the first simple, rapid and device-free test of its kind to detect heat-exposed substandard vaccines, making it a potential test for deploying at key points in the supply chain in warm and hot countries to check the integrity of vaccine cold-chain. Although this test does not replace the more definitive lot release assays such as potency assays, it could initially be used as a rapid and low-cost test to identify substandard sucrose-containing vaccines within supply chains, in support of WHO's Prevent, Detect, and Respond strategy.
维持冷链完整性对于疫苗至关重要，可确保其在常规储存和运输过程中保持在推荐温度范围内。这能保证疫苗的稳定性、有效性，并避免降解。在此，我们提出基于简单葡萄糖测定的快速低成本检测方法，以通过蔗糖在高温下固有地逐渐转化为葡萄糖来检测受热暴露而降解的含蔗糖疫苗。生物发光和比色测定以及用于尿液样本的临床生化分析仪可通过检测葡萄糖水平的显著升高成功确定热暴露对疫苗的影响。我们表明，葡萄糖的这种升高也与疫苗效力的丧失相关。当疫苗在37℃和45℃下孵育时，生物发光测定能够从热暴露12小时起检测到葡萄糖水平的升高。生化分析仪能够成功检测出暴露于37℃和45℃的新冠疫苗中升高的葡萄糖水平。最重要的是，比色测定的优点是只需将疫苗与试剂简单混合就能直观地产生颜色变化，无需酶标仪或任何其他复杂设备。据我们所知，这是同类中首个用于检测受热暴露的不合格疫苗的简单、快速且无需设备的检测方法，使其成为在温暖和炎热国家的供应链关键点部署以检查疫苗冷链完整性的潜在检测方法。尽管该检测不能替代诸如效力测定等更具决定性的批放行检测，但它最初可作为一种快速低成本检测方法，用于识别供应链中不合格的含蔗糖疫苗，以支持世卫组织的预防、检测和应对战略。
