Testing new vaccines with lab-grown mini-organs

Developing and testing new treatments or vaccines for humans almost always requires animal trials, but these experiments can sometimes take years to complete and can raise ethical issues about the treatment of animals. Now, researchers have developed a new test platform that encapsulates B lymphocytes—some of the most important components of the immune system—in organoids (“miniature organs”) to speed up vaccine screening and significantly reduce the number of animals needed.

The breakthrough is the work of a team made up of, among others, Tyler D. Moeller and Matthew DeLisa, from Cornell University, and Ankur Singh, from the Georgia Institute of Technology, both institutions in the United States.

Vaccines introduce an antigen into the immune system. The antigen can be part or all of a virus or bacteria, allowing the body to prepare for future exposure by programming its B cells to make antibodies against the antigen. However, certain bacteria coat themselves in a polysaccharide “disguise”, requiring specialized conjugate vaccines, such as those that protect against pneumonia and meningitis. In this type of approach, a piece of the antigenic polysaccharide is attached, or conjugated, to a carrier protein that the body can recognize. However, it is not yet known exactly how conjugate vaccines interact with B lymphocytes to induce an immune response.

The traditional way of testing vaccines is to inject them into animals and wait weeks or months for the result. Furthermore, when developing a new class of vaccine or focusing on a new target, scientists often have to evaluate many vaccine candidates, which requires extensive animal studies. To speed up the process and address ethical issues, the scientific community has begun to explore the use of organoids, which, in this case, are small collections of lymphocytes that act like miniature organs, creating a simulated environment that reflects the in vivo conditions. Hundreds of immune lymphocyte organoids can be built from the spleen of a single animal, greatly increasing assay throughput and could help researchers keep up with the sheer number of compounds they can create and need to test.

With all this in mind, Moeller and his colleagues wanted to see if this method would provide similar results to animal experiments and if the platform could be used to screen a large number of glycoconjugate-based vaccine candidates.

An already validated vaccine. (Photo: James Gathany/CDC)

To build organoids, the researchers isolated B lymphocytes from mouse spleens, added cell signaling molecules and structural components, and then encapsulated everything in a synthetic hydrogel matrix. Next, they prepared candidate conjugate vaccines against the bacterium responsible for tularemia, or “rabbit fever,” for which there is currently no approved vaccine. Candidates were tested using both traditional in vivo mouse assays and the new organoid platform. B cells reacted similarly in both formats and also provided information about the various biochemical changes that occur as the cells mature into antibody-producing cells. As a result, the team found that the platform could be used to identify B cell clones that generate highly specific antibodies against antigens, which has a wide variety of potential applications. While this work is preliminary, the researchers say the organoid platform could help reduce the time it takes to develop and test new conjugate vaccines.

The study is titled “Profiling Germinal Center-Like B Cell Responses to Conjugate Vaccines Using Synthetic Immune Organoids”. And it has been published in the academic journal ACS Central Science. (Source: American Chemical Society)