Scientists at the Pasteur Institute in France say they have developed artificial lymphoid organ-chips that recreate much of the human immune system’s response to booster vaccines. The technology, described in a study “Modeling memory B cell responses in a lymphoid organ-chip to evaluate mRNA vaccine boosting” in the Journal of Experimental Medicine (JEM), could potentially be used to evaluate the likely effectiveness of new protein and mRNA-based booster vaccines for COVID-19 and other infectious diseases, according to the researchers.
“Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a lymphoid organ-chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix,” write the investigators.
“Perfusion of the SARS-CoV-2 spike protein mimicked a vaccine boost by inducing a massive amplification of spike-specific memory B cells, plasmablast differentiation, and spike-specific antibody secretion. Features of lymphoid tissue, including the formation of activated CD4+ T cell/B cell clusters and the emigration of matured plasmablasts, were recapitulated in the LO chip.
“Importantly, myeloid cells were competent at capturing and expressing mRNA vectored by lipid nanoparticles, enabling the assessment of responses to mRNA vaccines. Comparison of on-chip responses to Wuhan monovalent and Wuhan/Omicron bivalent mRNA vaccine boosts showed equivalent induction of Omicron neutralizing antibodies, pointing at immune imprinting as reported in vivo.
“The LO chip thus represents a versatile platform suited to the preclinical evaluation of vaccine-boosting strategies.
“The COVID-19 pandemic has emphasized the need for preclinical systems that enable a rapid evaluation of immune responses elicited by candidate booster vaccines, particularly within specific cohorts of high-risk individuals,” says Lisa Chakrabarti, PhD, a group leader within the virus and immunity unit at the Institut Pasteur.
Secondary lymphoid organs
The immune system’s response to a vaccine is coordinated in secondary lymphoid organs, such as the lymph nodes and spleen, where various types of immune cell gather and interact with each other to spur the development of specific antibody-producing B cells. Chakrabarti’s team, led by postdoctoral researcher Raphaël Jeger-Madiot, PhD, created an artificial version of these organs by embedding small samples of human blood cells in 3D collagen matrices on tiny microfluidic chips. These lymphoid organ-chips can then be exposed to viral proteins and RNAs used in vaccines.
“The continuous perfusion of microfluidic chips with antigen and nutrients greatly facilitates the growth and activation of immune cells” explains Samy Gobaa, PhD, who leads the Pasteur Microfluidics platform and collaborated on the study.
When the researchers exposed the lymphoid organ-chips to the SARS-CoV-2 spike protein, B cells and T cells within the blood samples became active and clustered together, just as they do in real lymphoid organs. The B cells then matured and began to produce antibodies capable of neutralizing the SARS-CoV-2 virus.
By comparing lymphoid organ-chips created with blood samples from different donors, however, Chakrabarti and colleagues were able to observe a variety of different responses: chips created from some donors responded equally well to either type of mRNA booster, while chips created from other donors showed a stronger response for either the monovalent or bivalent vaccine.
“This illustrates the diversity of immunological histories in the population, and the resulting individual variability in vaccine responses,” says Jeger-Madiot.
“In the face of such variability, the lymphoid organ-chip could provide a useful preclinical system to evaluate the capacity of candidate vaccines to induce neutralizing antibodies against current SARS-CoV-2 variants in diverse human populations. This should be an asset in the face of a rapidly evolving SARS-CoV-2 pandemic,” adds Chakrabarti.
