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UMB-CCHI Overview

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Vaccines are widely viewed as cost-effective interventions to prevent and control classical endemic and epidemic infectious diseases, as well as to limit the transmission and impact of emerging infections and certain bioterror agents. However, the development of new and improved vaccines against some of these agents is hampered by a lack of information concerning the "true" (i.e., operative) immunological mechanisms underlying the protection elicited by natural infection and by candidate vaccines.

This is particularly true with regard to pathogens that enter the host via mucosal surfaces, including the gastrointestinal (GI) tract. Thus, the UMB-CCHI is focused on furthering our understanding of the protective immunological mechanisms that can be elicited in the GI microenvironment of humans. Moreover, because the normal GI flora (microbiota) is certain to influence the host immune response, we are conducting pioneering studies on the interactions between the local intestinal microbiota and the host immune response in humans.

We are focusing our efforts on in-depth studies of three major gram negative bacterial human pathogens, including Helicobacter pylori, Salmonella enterica serovar Typhi and Shigella, each primarily affecting a distinct major segment of the GI tract (i.e., the stomach, ileum and colon, respectively). Because virtually all of the limited information available concerning the determinants of protective mucosal immunity comes from studies in adults, we will also focus some efforts in exploring the responses to oral immunization with the licensed Ty21a typhoid in children and, for the first time, the elderly.

In addressing the complexity of this undertaking, we have assembled a multidisciplinary team consisting of renowned investigators in the fields of innate and adaptive immunity, molecular biology, mucosal biology and physiology, biochemistry, high-throughput technology, microbiology, genomics, protein chemistry and clinical gastroenterology and vaccinology (with extensive experience in performing endoscopies and in conducting vaccine trials).

In addition, we are developing two novel technologies to broadly advance the study of human immunology, including a human-based approach to study the entire S. Typhi ORFeome to identify CD8+ T cell responses and a peptide conformation constrainment technology and potential mucosal adjuvants to advance H. pylori vaccines. We expect this CCHI to yield much-needed information in an area of great importance to human health.