Viral infections are a significant cause of morbidity and mortality and burden society with billions of dollars each year in health care costs and lost productivity at work and school. Thus, vaccines and treatments for the common viral pathogens as well as the less common, but potentially devastating viruses, are urgently needed. However, our understanding of the key molecular and cellular mechanisms involved in regulating immunity to naturally acquired viral infections and anti-viral vaccines is still quite limited. In particular, despite knowing that T cells and B cell-derived antibodies play critical roles in vaccine-mediated protection to viruses, we know remarkably little about how the protective subsets of virus-specific B and T cells are generated and maintained following natural infection and even less regarding how to rationally design vaccines that will elicit these protective subsets. Likewise, we do not know whether the molecular pathways and "rules" that control the generation or maintenance of virus-specific protective T and B cells are different in mucosal versus systemic sites or whether the rules change following chronic versus acute virus infections. The goals of Core B are to develop, characterize and distribute virus-specific tools that will be used by all of the Projects to address these important questions. Specifically, Core B will generate, characterize and maintain virus stocks for experimental infections. Core B will produce and purify viral proteins that will be used to restimulate virus-specific T and to detect virus-specific antibody and antibody secreting cells. Finally, Core B will generate novel fluorochrome-labeled "B cell tetramers" that will be used by Project investigators to identify, enumerate and characterize virus-specific B cells ex vivo using flow cytometry. Thus, the reagents generated by Core B will allow the investigators in this U19 Program to analyze at a single cell level how B and T cell fate decisions impact the development and maintenance of protective anti-viral immune responses following infection and vaccination. Collectively, the Aims of Core B will promote synergy and cooperation between Projects and accelerate the pace of research by relieving the Projects from the burden of reagent development and production
The reagents generated in Core B will facilitate the identification and functional characterization of virus specific B and T cells following infection with viruses that cause chronic and acute infection of mucosal and systemic sites. Experiments using these reagents will increase our understanding of how lymphocytes (or white blood cells) protect us from virus infections and will allow us to design better vaccines.