The threat of pandemic disease caused by emerging infectious organisms is an immediate and ongoing concern. Many emerging pathogens (Ebola virus, avian influenza) cause disease for which no effective post-exposure treatment exists. Thus, development of vaccine vector platforms is a priority. The goal of this project is to compare multiple vectors to determine which is best suited for developing vaccines against emerging infections. This study compares humoral immune responses generated after immunization of mice with the following vaccine vectors expressing cowpox B5R: DNA, recombinant adenovirus, recombinant vesicular stomatitis virus, M. smegmatis, modified vaccinia Ankara, and Venezuelan equine encephalitis virus replicon particles. Vectors were tested in heterologous prime/boost combinations, using ELISAs to quantify anti-B5R antibody in the serum of immunized mice. At three months post boost animals were challenged with vaccinia WR to evaluate protection. We report here that of the seven priming vectors tested, rAd5-B5R generated the highest initial titers to B5R. At six weeks post primary immunization mice were boosted with either rAd5-B5R or rVSV-B5R. After boosting most animals (regardless of priming vector) had significantly increased serum antibody titers to B5R which persisted until the time of challenge. The prime boost combinations generating the highest anti-B5R titers by four weeks post boost were: rAd5 prime/rVSV boost, protein prime/rAd5 boost, and protein prime/rVSV boost. Titers were not significantly different between these three prime/boost groups, but all generated significantly higher titers than the other ten combinations tested. In general, titers of rVSV boosted animals increased to levels significantly higher than those achieved via immunization either with the priming vector, or with rVSV alone, indicating a synergistic effect of the prime/boost. In contrast, titers of rAd5 boosted animals rarely increased above titers of animals receiving rAd5 alone, indicating that rAd5 may be used optimally as a priming, rather than a boosting vector. In a second trial we delivered vaccine vectors intranasally rather than intramuscularly. This trial included only rAd5, rVSV, and VEE-VRP vectors. Intranasal delivery increased immunogenicity of all vectors tested, with VSV prime- VRP boosted animals having the highest overall titers. Relevance to Public Health: Safe and effective vaccines for a variety of emerging diseases such as avian influenza, Ebola virus, and West Nile virus are urgently needed. The goal of this project is to identify the best vaccine platforms or vectors for making human vaccines. Information gained in this project should allow researchers to pick the best vaccine platform for a certain disease, and should also decrease the time it takes to bring a new vaccine into public use.
Showing the most recent 10 out of 400 publications
