Artificial lymphoid organ-chips developed to accurately predict vaccine responses have now become available to humans.

Researchers from France’s Institut Pasteur have developed artificial “lymphoid organ-chips,” replicating much of how humans respond to booster vaccines. According to an upcoming publication of Journal of Experimental Medicine (JEM), this technology could potentially be used for testing new protein or mRNA-based booster vaccines against COVID-19 as well as other infectious diseases.

Due to SARS-CoV-2 and other viruses’ rapid mutation and evolution, booster vaccines must also evolve quickly in order to provide protection from new viral strains. Unfortunately, its efficacy can often be hard to predict; recently the bivalent mRNA COVID vaccine proved no more effective against Omicron variant than its monovalent predecessor; one factor may have been laboratory animals having different immune systems than humans being used for testing vaccines; another possibility may have been how an individual responds depending on his/her history with infection and vaccination experiences; individuals’ responses also vary significantly according to individual history with infection/vaccine treatments over time and vaccination experiences over time and history if ever introduced at all.

The COVID-19 pandemic has demonstrated the necessity of preclinical systems allowing rapid evaluation of immune responses elicited by candidate booster vaccines, particularly within cohorts at higher-than-usual risk of COVID infection.
Lisa Chakrabarti of Institut Pasteur’s Virus and Immunity Unit.

Chakrabarti and team, led by postdoctoral researcher Raphael Jeger-Madiot of his laboratory at Columbia, created an artificial version of these organs by embedding human blood cells in 3D collagen matrixes on microfluidic chips; once complete, these lymphoid organ-chips may then be exposed to viral proteins and RNAs used as vaccines.

Samy Gobaa of Pasteur Microfluidics platform and one of its collaborators on the study noted: “Continuous perfusion of microfluidic chips with antigen and nutrients greatly facilitates immune cell activation”, says Gobaa.

Researchers found that when exposed to SARS-CoV-2 spike protein, B cells and T cells within blood samples became active and clustered together like they do in real lymphoid organs, while matured B cells produced antibodies capable of neutralizing SARS-CoV-2 virus.

Human blood samples containing multiple immune cell types enabled lymphoid organ-chips to respond effectively to COVID vaccines that used mRNA technology, just as in real world results; similarly, bivalent vaccines weren’t any more successful at inducing Omicron-neutralizing antibodies than monovalent ones in producing such responses.

Chakrabarti and colleagues created lymphoid organ-chips from blood samples donated from different donors, to observe various responses; chips created from some donors responded equally well to both types of mRNA boosters; while those made using samples from others showed significantly stronger reactions toward either monovalent or bivalent vaccines.

“This illustrates the diversity in immunological histories within populations, leading to individual variation in vaccine responses,” according to Raphael Jeger-Madiot.

“Considering such variability, lymphoid organ-chip could serve as a valuable preclinical system to evaluate candidate vaccines’ capacity to induce neutralizing antibodies against SARS-CoV-2 variants that currently circulate across human populations,” notes Chakrabarti. Such evaluations should prove invaluable against an ongoing pandemic afflicted by this virus.
Rockefeller University Press Journal Reference:Jeger-Madiot, R. et al (2024). Modeling memory B cell responses using lymphoid organ-chip technology to evaluate mRNA vaccine boosting. Journal of Experimental Medicine; DOI 10.1084/jem.20240289.