Although there is intense interest in improving vaccine design and efficacy, these efforts are hampered by a lack of knowledge about how human immune responses are coordinated and developed inside lymphoid tissues. The vaccine development process is traditionally empirical, expensive, labor-intensive, and slow, making it difficult to rapidly respond to pandemics and pathogens of global concern. Though blood-based assays are becoming increasingly sophisticated, these methods often fail to identify strong correlates of protection for many of the deadliest pathogens of our time as many important cell types that are responsible for developing adaptive immunity are not found in peripheral blood. One way to circumvent this problem is to use organoid technologies that recapitulate the major features of adaptive immunity in vitro for infection and vaccine testing.
Immune organoids can be produced from human tonsil tissues, spleen, and lymph nodes. These organoids respond appropriately to influenza vaccines and viruses and recapitulate many of the key features of the adaptive response, such as differentiation of B cells into plasmablasts, T cell activation, and specific antibody secretion. The major goals of the Wagar lab are to 1) expand this vaccine work to other infectious diseases such as SARS-CoV2, 2) unravel mechanisms involved in regulating human adaptive immunity, and 3) explain inter-individual variability in vaccine responsiveness. It is our hope that engineering strategies to help us dissect the mechanistic aspects of human immunity will accelerate and inform vaccine design.
The mission of the Wagar lab is to accelerate vaccine design and immunotherapies to ultimately understand, treat, and prevent human disease.