Scientists are accelerating vaccine testing by using organoids. This approach, highlighted by the American Chemical Society, mirrors how real human tissues respond while reducing the need for animal experiments. Vaccines work by exposing the immune system to a safe version of an antigen so the body learns to recognize it. This training helps B cells, which are a type of white blood cell, produce antibodies that can neutralize the antigen in future exposures. Some bacteria wear a polysaccharide shield that makes this process more challenging. To overcome that, researchers rely on special conjugate vaccines that link the polysaccharide to a carrier protein, enhancing the immune signal and prompting a robust antibody response. Yet the exact way a conjugate vaccine engages B cells to trigger immunity is not always fully understood, creating a gap in our mechanistic knowledge.
Traditionally, new vaccines of this kind undergo lengthy animal testing. That pathway can be slow and raises ethical concerns due to the large number of animals required. In response, a team led by Matthew DeLiza and colleagues explored organoid technology as a partial substitute for animal experiments. Organoids are tiny, self-organizing miniatures of human or animal organs created from living cells. They can recapitulate important features of tissue structure and function, offering a controlled environment to study immune reactions. In this work, immune cell organoids were generated from splenic tissue, enabling researchers to observe how B cells respond to a vaccine in a setting that resembles the living organism but without using whole animals. Creating hundreds of these immune cell organoids from a single animal spleen dramatically increases testing throughput and provides a reproducible platform for comparing responses across different vaccine formulations.
The team obtained B cells from mouse spleens and cultured them with signaling molecules and structural cues, then encapsulated them within a synthetic hydrogel shell. This hydrogel mimics the supportive environment of tissues, allowing the B cells to organize and communicate as they would in vivo. The researchers then conducted comparative experiments by delivering an experimental conjugate vaccine for tularemia into both live mice and the organoid models. The goal was to determine whether the B cell response would track closely between the two systems, which would validate organoids as a meaningful surrogate for early vaccine testing. The results showed that the B cells in the organoids recognized the conjugate vaccine and produced antibodies in a manner consistent with responses observed in living mice. This alignment supports the potential of organoid-based assays to streamline vaccine development while reducing animal use and speeding the evaluation process.
While these findings are a significant step forward, ongoing work will refine how closely organoids replicate the full complexity of immune responses across diverse individuals. Researchers are exploring ways to incorporate additional cell types and tissue features to capture nuances of tolerance, memory formation, and long-term protection. The prospect is encouraging: organoid technologies could become an integral part of the preclinical toolkit, offering rapid, ethically conscious, and scalable testing options for vaccines that rely on polysaccharide antigens and other challenging targets. The broader implication is clear—scientists are continually expanding the toolkit that accelerates safe and effective vaccines for global health, including populations across North America. In time, organoid platforms may help reduce the uncertainties of early vaccine testing and accelerate the journey from laboratory insight to clinical impact, all while maintaining rigorous safety standards and high-quality science.