Ensuring vaccine cold chain integrity: A rapid and low-cost test for identifying heat-exposed sucrose-containing vaccines

Maintaining cold-chain integrity is vital for vaccines to ensure they remained within the recommended temperature limits to ensure stability and avoid degradation as storage temperature is one of the key factors contributing to rendering products substandard or ‘out of specification’. Heat-exposed vaccines closely resemble the chemical composition of the stable product making them very difficult to detect and testing as such is not routinely carried out at various points in the supply chain due to the lack of tools to identify effects of heat exposure in the field, a particular issue in countries with high-temperature climates. Here, we propose rapid and low-cost tests based on simple glucose assays to detect heat-exposed degraded sucrose-containing vaccines through its inherent gradual conversion to glucose at elevated temperatures. Bioluminescent and colorimetric assays and a clinical biochemical analyser for urine samples could successfully determine effects of heat exposure 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 hours of heat exposure. The biochemical analyser could successfully detect if a COVID-19 vaccine had been exposed to 37 and 45°C. Most importantly, the colorimetric assay has the advantage of noticing a colour change by eye 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 device-free test of its kind to determine the heat-exposed vaccines, making it an ideal test for deploying at various points in the supply chain in low- and middle-income countries to ensure the integrity of vaccine cold-chain. Although this test does not replace the more definitive 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.