ELISpot: A Sensitive Tool for Monitoring Unwanted Immunogenicity Across Drug Development

Christine Bain, Ph.D. December 15, 2025

Originally developed to monitor B cells producing antigen- or pathogen-specific antibodies, the ELISpot assay is widely used for evaluating vaccine-induced wanted immunogenicity. However, thanks to its high sensitivity, it is also a valuable tool for investigating unwanted immunogenicity, expanding its applications beyond traditional vaccine research.

Early Applications in Preclinical Development

During the preclinical phase, ELISpot supports early immunogenicity risk assessment for biotherapeutics, often when combined with in silico and complementary in-vitro assays. This approach helps developers anticipate and mitigate unwanted immune responses before entering clinical stages, strengthening the overall safety profile of candidate drugs [1].

Monitoring Immune Responses in Early Clinical Trials

In early clinical development, ELISpot is essential for evaluating immune responses to advanced therapies, including cell and gene therapies. These responses may target the viral vector, most often the adeno-associated virus (AAV) capsid, the encoded transgene product, or the chimeric antigen receptor (CAR) in CAR-based cell therapies. ELISpot is also used to monitor unwanted Th1 T-cell immunogenicity in vaccine programs aiming at eliciting humoral responses, such as Amyloid-beta vaccines administered to patients with Alzheimer’s disease, where excessive T-cell responses may be harmful [2].

Post-Market Safety and Hypersensitivity Assessment

Even for marketed drugs, ELISpot is being evaluated as a predictive tool for identifying individuals at risk of severe hypersensitivity reactions, such as those caused by certain antibiotics [3].

Conclusion

From early discovery to post-market surveillance, ELISpot has evolved into a versatile and essential technology for assessing both wanted and unwanted immunogenicity. Its sensitivity and adaptability continue to make it a reliable tool in the development of safer and more effective therapeutics.

References

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