Lab-grown mini organs promise quick vaccine testing with fewer animal trials

Miniature organoids for quick vaccine screening

The first coronavirus case was reported in December 2019 and by the time the first COVID-19 vaccine was approved for public use in December 2020, about 1.8 million people had already died across the globe. 

Developing a vaccine suitable for human use within one year of the outbreak was a remarkable achievement. However, there is no doubt many many more lives could’ve been saved if we had a faster vaccine screening process. 

During standard vaccine trials, first a vaccine is injected into the body of an animal, and then scientists wait for weeks and sometimes for months to examine the results. Then they test the vaccine on other animals and this process is repeated until the vaccine becomes 100 percent safe for human trials.

This process sometimes takes years to complete and during this time, many animal subjects had to live with both the good and bad side effects of the vaccine. The researchers suggest that instead of using numerous animal models, vaccines can be screened using organoids —- lab-grown cell clusters that collectively behave like a mini organ. 

“Hundreds of immune cell organoids can be constructed from the spleen of a single animal, greatly increasing testing throughput — which could help researchers keep up with the large numbers of compounds they can create and need to screen,” the study authors note. 

How does a mini organ test vaccines?

When a vaccine (containing a virus or a bacteria) enters the human body, the foreign molecules or antigens carried by the pathogen start attacking the immune system. In response, the immune system directs its B cells (a type of white blood cell) to start producing antibodies to kill the antigens.

The mini-organs developed by researchers during the study are made up of a hydrogel matrix comprising B cells extracted from mice spleens and some signaling molecules. They used these organoids to test some rabbit fever vaccines. 

Rabbit fever is an infection caused by Francisella tularensis bacteria. Humans can catch this disease either by coming in contact with an infected rabbit or by the bite of a fly carrying the bacteria. Currently, there is no approved vaccine for rabbit fever. 

The researchers selected some rabbit fever vaccine candidates and tested the same using organoids as well as traditional mice trials. Interestingly, B cells in organoids and in real mice responded to the antigens in the same way. The study reveals that In both cases, a roughly equal number of carrier-specific antibodies were produced.

These findings strongly suggest that lab-grown organoids have the potential to emerge as a great alternative to contemporary vaccine screening methods. The researchers claim that although this approach is in its initial phase, it can surely reduce the time and number of animals required for testing new vaccines. 

The study is published in the journal ACS Central Science.

Study Abstract: 

Glycoengineered bacteria have emerged as a cost-effective platform for rapid and controllable biosynthesis of designer conjugate vaccines. However, little is known about the engagement of such conjugates with naıvë B cells to induce the formation of germinal centers (GC), a sub-anatomical microenvironment that converts naıvë B cells into antibody-secreting plasma cells. Using a three-dimensional biomaterials-based B-cell follicular organoid system, we demonstrate that conjugates triggered robust expression of hallmark GC markers, B-cell receptor clustering, intracellular signaling, and somatic hypermutation. These responses depended on the relative immunogenicity of the conjugate and correlated with the humoral response in vivo. The occurrence of these mechanisms was exploited for the discovery of high-affinity antibodies against components of the conjugate on a time scale that was significantly shorter than for typical animal immunization-based workflows. Collectively, these findings highlight the potential of synthetic organoids for rapidly predicting conjugate vaccine efficacy as well as expediting antigen-specific antibody discovery.