To be effective, vaccines should induce immune responses, not only of an appropriate magnitude, but also of the appropriate quality. This will vary, depending on the nature of pathogen vaccination. The quality of a humoral response is determined by the distribution of immunoglobulin isotypes amonth the antibodies elicited. Current opinion holds that the profile of isotypes expressed by responding B cells is directed by diffusable regulators (cytokines). This consensus predicts that the response to a given immunogen in an individual should be affected in a coplex manner by reactions to other antigens occurring simultaneously in that individual. In contrast, recent observations indicate that simultaneous immune responses can be separated into distinct compartments, functionally insulated from one another. The long-term objectives of the proposal is to determine how such compartments are generated, and how they can be manipulated to optimize vaccine efficacy.
Specific aims i nvestigate whether immune compartments result from the activity of distinct sets of antigen-transporting cells, by purifying such cells, exposing them to infectious or inactivated viral vaccines, and determining the quality of immunity generated by the cell populations after reinjection into mice. Parallel experiments dissect the helper T cell response to viral antigens presented by the different populations of antigen presenting cells. Features of vaccine design and delivery are probed to discover conditions that result in the breakdown of the compartmental barriers that insulate immune responses, so as to develop a rational basis for optimal manipulation of vaccines.
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