A Novel Omics Assay to Measure the Functionality of the Innate Immune System Using Spectral Flow Cytometry

The innate immune system plays a pivotal role in defense against pathogens via pattern recognition receptor sensing, initiating responses upon infection or vaccination. Understanding the functional capacity of this system is crucial for deciphering correlates of vaccine efficacy and assessing responses to infection.

A holistic approach was developed to study immune function, generating >3,100 readouts across 16 cell types, 18 pattern recognition receptors, and 11 cytokines using spectral flow cytometry. To explore geographical variation, the study evaluated the immune responses of European donors, as well as samples from urban and rural Indonesian individuals. There were differences observed in the outcomes, including increased IL-1β production and impaired IFN-γ production by innate lymphocytes following TLR8 stimulation in the rural Indonesian cohort. In the European cohort vaccinated with mRNA-1273, baseline IFN-γ production by innate lymphocytes correlated with SARS-CoV-2 spike-specific immune responses. In vitro mRNA vaccine stimulation also induced IFN-γ production, which was TLR8-dependent and reduced in the rural Indonesian group.

In summary, an approach to study the functional capacity of the immune system was developed, exploring geographical variation and mRNA vaccine responses. The results revealed TLR8's potential role in responding to mRNA vaccines and an impairment in this pathway in rural Indonesian individuals.