The long term objective of this study is the development of an effective delivery system for a live human rotavirus vaccine. In order to avoid the inactivation of virus by gastric acid, different buffers are being given before vaccination in current vaccine trials. However, this procedure is time consuming and increases the cost of vaccine delivery. this proposal is focused on the improvement of this vaccine administration procedure by encoating live vaccine with enteric polymer to protect viruses from gastric acid. It has been shown in the Phase I study that live porcine rotavirus coated with anenteric polymer retained infectivity and was protected from inactivation with acid treatment. In Phase II, we plan to further improve the formulation for enteric encapsulation by examining different ingredients for core particles as well as modified procedures for enteric coating of virus-containing core particles. The enterically coated viruses will be tested for their stability against acid treatment. The coated virus will be then orally administered into gnotobiotic piglets to examine their ability to multiply in the intestinal tract. The immune response as well as the protective ability of the enterically coated virus will be examined. Once the most effective formulation is established, human rotavirus vaccine will be coated by the same procedure and evaluated in vitro followed by an in vivo human clinical trial collaboration of Dr. A.Z. Kapikian at NIH.
| Moissoglu, Konstadinos; Kiessling, Volker; Wan, Chen et al. (2014) Regulation of Rac1 translocation and activation by membrane domains and their boundaries. J Cell Sci 127:2565-76 |
| Gregory, Sonia M; Harada, Erisa; Liang, Binyong et al. (2011) Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2. Proc Natl Acad Sci U S A 108:11211-6 |
