Research Project
6374650
Numerous studies have shown that viral epitopes and subunits of bacterial toxins can be expressed and correctly processed in transgenic plants to yield immunologically active antigens for vaccine use. These recombinant immunogens have numerous benefits over current vaccine technologies, including safety, economy, stability, versatility and efficacy. Antigens expressed in maize seed are particularly advantageous since the seed can be grown in vast quantities and shipped over long distances at ambient temperature potentially making possible the vaccination of global populations. The expression of immunogens in maize also makes possible the development of edible vaccines that effectively stimulate the mucosal immune system upon consumption. The mucosal immune system is often the best first defense against many transmissible diseases entering the body through oral, respiratory and urogenital routes. The overall objective of this research is the application of transgenic plant technology to the search for a vaccine against the human immunodeficiency virus (HIV). Recent HIV vaccine research has focused on the stimulation of mucosal immunity in an attempt to protect against HIV infection. To date, however, there have been no reports of the use of transgenic plant technology in HIV vaccine research. The major HIV envelope glycoprotein, gp120, plays a central role in the study of subunit vaccines against HIV, and the related simian virus, SIV. The overall objective of the current research will focus on the expression of the SIVmac239 gp120 subunit in transgenic maize. The generation of transgenic maize expressing this subunit will serve as a model to evaluate the use of this technology in the development of HIV vaccines. The gp120-coding region will be optimized for maize expression and used to transform maize through an Agrobacterium-mediated transformation system. Western blot and ELISA techniques will be used to evaluate transgenic maize for recombinant gp120 expression. Attainment of the long-term object of this study will result in the generation of transgenic maize seed that can be used as a reagent for SIVmac239 pathogenic challenges in primates. The plant material thus obtained would potentially serve as a model for stand-alone edible vaccine, as a booster vaccine, or for use in combination with other vaccines including killed or attenuated strains, parenteral vaccines, and DNA vaccines. This application will serve as a model for the exploration of the use of this methodology to develop HIV vaccines, potentially against a number of important HIV epitopes, for the control of HIV infection.
