The human immune response to infection and immunization - Profiling via modern immunological methods and systems biology. The Hepatitis B subunit vaccine induces immunity in millions of people by inducing antibodies that prevent viral infection. However, the variability in the antibody response to the Hepatitis B surface antigen (HBS) component of the vaccine in different individuals is remarkably large and some individuals fail to respond altogether. We propose that this variability provides a golden opportunity to understand the diversity of human immune responses to vaccination and identify immune response correlates. The central hypothesis of this application is that the number of naive antigen-specific B cells and/or CD4+ helper T cells in the pre-immune repertoire dictates the magnitude of the antibody response. We will test this hypothesis using an ultra sensitive method that we developed to detect HBS-specific B cells and HBS peptide-Major Histocompatibilty Complex II-specific CD4+ helper T cells in humans before and after vaccination. The goals of this proposal are to develop the reagents needed for comprehensive analysis of the HBS-specific naive T and B cells in humans and then use these tools to determine whether or not the great range in postvaccination antibody titer is explained by variations in the pre-immune repertoire. This innovative approach could provide the ultimate biomarker of vaccine response - the vaccine-specific lymphocytes themselves - and provide direction as to how the vaccine could be improved to protect all individuals.
These studies are relevant because they have the potential to explain why certain people do not develop specific antibodies after receiving the Hepatitis B subunit vaccine. Our theory is that these individuals lack the relevant lymphocytes before vaccination. If this theory is correct, then these individuals should develop antibodies if vaccinated with a different Hepatitis B subunit. Therefore, these studies have the potential to predict who will not respond to this important vaccine and suggest a solution to this problem.