Gastroenteritis is a worldwide infectious disease problem that is the major cause of neonatal and infant mortality in developing countries and of significant morbidity in developed countries. Recognition that rotaviruses and enterotoxigenic Escherichia coli are the major agents that cause lifethreatening disease has focused vaccine development against these pathogens. The objective of the proposed work is to test the use of purified rotavirus capsid proteins as orally administered intestinal immunogens. This project will evaluate the ability of rotavirus capsid proteins (VP3, VP6 and VP-7) synthesized in high yields in a baculovirus expression system to induce a mucosal immune response and to be used as a vaccine. Purified expressed proteins will be evaluated as immunogens in two animals models of rotavirus gastroenteritis and in volunteers. Passive protection will be tested in a mouse model, active protection will be tested in a rabbit model, and the immunogenicity of vaccines found to be active in these animal models will will also be tested in volunteers. Vaccine dose, formulation (individual or mixtures of proteins), and type of adjuvant used for oral immunization will be evaluated to determine their effectiveness in stimulating both mucosal and systemic immunity and protection from virus challenge. These studies will directly assess the use of purified rotavirus proteins as rotavirus proteins as rotavirus subunit vaccines. The results will also be tested for their general applicability for the development and use of purified proteins from other enteric pathogens as mucosal vaccines.
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