Senior Scientist Applied Biotechnology Institute San Luis Obispo, California
Body of Abstract: Lyme Disease (LD) is caused by Borrelia burgdorferi (B. burgdorferi) and is spread by Ixodes sp. ticks to humans. Small reservoir rodents such as mice maintain the spirochete in its enzootic cycle. While this zoonotic disease is treatable if identified promptly, it is often not diagnosed soon enough and can lead to a number of long-term debilitating health problems. It is a major concern in the Northeast and Midwest, and the number of cases continues to rise. A recent CDC report estimates over 400,000 cases per year. Given the complexity of the problem, there is continued interest in development of next generation vaccines to break the enzootic cycle of B. burgdorferi. These vaccines can be applicable to humans, companion animals, and to the wildlife reservoir. Ideally, a subunit vaccine is preferred because of its inherent safety benefits. The outer surface protein A (OspA) of B. burgdorferi is one immunogen used to develop a transmission-blocking vaccine. Plant-based systems can provide thermostable oral vaccines that are also stable in the digestive tract at a very low cost. In this work we proposed to overcome previous barriers by using new technology for expression of B. burgdorferi OspA in maize grain to develop a system for low-cost production of a proven transmission blocking vaccine against Lyme borreliosis. Our goal is to demonstrate protection from tick-challenge using a maize-based vaccine for a tick-borne transmitted bacterium, which has never been done before. Four constructs of the OspA protein were prepared. One is targeted to the endoplasmic reticulum (ER) and the other to the cell wall. Constructs were also prepared replacing the native signal sequence of OspA with a plant-specific sequence that allows lipidation in a plant system. These constructs were introduced into maize and analyzed for high expressing lines.