Systems Analyses of the Immune Response to the Seasonal Influenza Vaccine

Certain functions of the immune system are revealed only when the immune system is challenged. When a person is vaccinated, a coordinated response results: activation and interaction of distinct innate and adaptive immune cell populations and pathways, culminating in the formation of germinal centers from which antibody-producing plasma cells and memory B cells derive. By taking measurements at various time points before and after vaccination, we can build a comprehensive picture of how the immune system responds to a vaccine challenge.

The seasonal influenza vaccination provides an excellent model of coordinated immune activity involving innate and adaptive responses, as demonstrated in a past NIH study in 2009-2011; however, scientific advances and the possibility of multi-season responses in individuals warrant a new follow-up study with more comprehensive sampling. This is an open-label, prospective, exploratory study to assess the baseline and post-vaccination immune responses of healthy volunteers to an approved seasonal influenza vaccine. Subjects will undergo baseline blood collections on day -7 and on day 0 before receiving the study vaccine. After vaccination, blood will be collected on days 1, 7, 14, 28, 70, and 100. Optionally, subjects may also give blood once a month, as requested, up until 1 year after vaccination. Blood samples will be used to assess short- and long-term immunological effects of immunization. Evaluations will include vaccine antibody titers. Additional evaluations may include peripheral immune cell phenotyping, RNA sequencing (RNA-seq) of whole blood and defined peripheral blood cell subsets, and measurement of serum proteins and antibodies. Subjects may optionally provide stool samples at some visits for exploratory microbiome assessment. Additionally, subjects may optionally continue study participation annually through the 2023-24 influenza season.

The goal of this protocol is to use the collective information gathered across all healthy volunteers to understand how the immune system works as a whole.