The two awardees of the 2008 PHPID Pilot Research Grant are:

1. Jianrong Li, DVM PhD
College of Food, Agricultural, and Environmental Sciences/College of Public Health with collaborators in College of Veterinary Medicine and College of Medicine

Title: Vesicular stomatitis virus as the vector to deliver human Norovirus virus-like particles: a new vaccine strategy against non-culturable foodborne viruses.

Abstract: Human Norovirus (HuNoV) is a major causative agent of foodborne gastroenteritis worldwide.Currently, there are no vaccines or effective therapeutic interventions for this virus. Generally, live attenuated vaccines stimulate strong systemic immunity and provide durable protection due to the continued expression of full viral proteins. Development of an attenuated vaccine for HuNoV has not been possible because it does not grow in cell culture. In this situation, a vectored vaccine may be ideal. It is known that expression of HuNoV capsid (VP1) protein, alone, results in virus-like particles (VLPs) that are structurally and antigenically similar to native HuNoV. The objective of this proposal is to develop vesicular stomatitis virus (VSV) as the vector to deliver a HuNoV VLP vaccine and to explore the 70-kDa heat shock protein (HSP70) as a potential immuno-enhancer for Norovirus vaccine. The Specific Aims are: (1) to generate recombinant VSV expressing HuNoV capsid and/or HSP70 proteins; (2) to determine whether VP1 assembles into VLPs using VSV as the vector; and (3) to determine whether VSV-based vaccine induces a specific immune response and whether HSP70 enhances the immune response in a mice model. This recombinant system will not only provide a new avenue for the development of vaccines for non-cultivable foodborne viruses, but also may lead to discover a
new adjuvant, HSP70, for Norovirus vaccine.

2. Ian Davis, DVM PhD
College of Veterinary Medicine with collaborators in College of Medicine and College of Pharmacy

TITLE: Nucleotide synthesis inhibitors as novel therapies for hypoxemia induced by influenza virus infection.

Abstract: This proposal will build upon our recent studies demonstrating that influenza virus inhibits alveolar fluid clearance (AFC) in BALB/c mice by a nucleotide-mediated mechanism. Studies examining effects of influenza infection on ion transport by primary human airway epithelial cell monolayers will show that these findings have relevance to human lung. The efficacy of nucleotide synthesis inhibitors will be tested in vitro and in vivo, to determine whether these agents might be developed as therapies for lung edema and hypoxemia in influenza-infected patients. Relevance: Influenza is of significant concern to human and veterinary public health. The nucleotide synthesis pathway, which our studies indicate is central to AFC inhibition by influenza virus, is a novel molecular target for influenza therapy. This proposal will test new influenza therapeutics based on this target. Impact: Influenza virus causes highly contagious acute respiratory disease that affects approximately 20% of all children and 5% of adults worldwide each year, with significant morbidity and mortality. A successful therapeutic based on this novel target would have a significant impact on influenza morbidity and mortality. Expected outcomes: Pharmacologic blockade of ion transport inhibition by influenza virus may reduce the severity of pulmonary edema and hypoxemia associated with this infection.