Immune Responses to Influenza Vaccination

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The development of accurate models that permit prediction of biological responses upon perturbation has the potential to increase our mechanistic understanding of pathophysiology and contribute to the development of improved therapeutics. The human immune system provides an excellent context for developing such systems biology approaches: many immune cells and molecular components are readily accessible from blood, permitting collection of samples from individuals across multiple time-points, followed by in depth data generation and analyses. Furthermore, there is an increasing understanding that the immune system and inflammation contribute to the pathogenesis of multiple disorders. These include not only those classically considered to involve the immune system such as autoimmune and infectious diseases, but also cancer, cardiac disease, diabetes, obesity, neurodegeneration, and other chronic illnesses affecting a large segment of the population (Germain and Schwartzberg, Nat Immunol. 2011). Thus, a more comprehensive and quantitative understanding of how immune responses are orchestrated, together with identification of predictive molecular and cellular parameters of effective vs. damaging responses, could have major implications for the prevention and treatment of diverse diseases. To this end, I helped coordinate one of the initial studies from the NIH Center for Human Immunology designed to help build a data base of normal human variation (the human immunome) and understand how variation in immune states contributes to immune reponses and disease (Tsang, Schwartzberg et al, Cell 2014; DIckler, H. et al, Ann New York Acad Sci, 2013). As a follow-up to these studies, Dr. John Tsang's laboratory has performed CITESeq technology to uncover specific cellular contributions to baseline states (or set points) that contribute to responsiveness to vaccines (Kotliarov et al Nat Med 2020). Strkingly, these same signature can predict severity of certain types of Luus. We are also conducting analyses from a follow-up study comparing responses to both an unadjuvanted and an adjuvanted vaccine against Influenza H5N1. To complement our work, we have added new assays, including the use of CITE-Seq. We are using these approaches to look at responses to immunization in greater depth and to optimize technical and scientific approaches to better understand what generates productive responses to vaccines and signatures associated with adjuvants.