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. Blood-based assays are becoming increasingly sophisticated, but these methods often fail to identify strong correlates of protection for many of the deadliest pathogens of our time because several important cell types that are involved in orchestrating the adaptive immunity are not detectable in peripheral blood. One way to circumvent this problem is to use in vitro organoid technologies that recapitulate the major features of human adaptive immunity.

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, 2) unravel mechanisms involved in regulating human adaptive immunity, and 3) explain inter-individual variability in vaccine responsiveness. We approach these questions from the perspective of the host and the perspective of the antigen design. It is our hope that engineering strategies to help us dissect the mechanistic aspects of human immunity will accelerate and inform vaccine design.

The lab has several active, funded projects:
-Predicting immunogenicity using human tonsil organoids
-Sex-based differences in vaccine and adjuvant responses
-Elucidating the effects of immune therapeutics in normal and tumor organoids
-Understanding differences in adaptive immunity (and repertoires) between tissues and the periphery
-Exploring the effects of adjuvants on vaccine protection and durability