Liposomal Adjuvant for Vaccine Development

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Advances in the development of genetically engineered vaccines to prevent outbreaks of infectious disease have prompted a re-evaluation of vaccination strategies against a number of pathogens. We have been developing a new model of immunization that is based on a flexible antigen delivery platform technology that provides highly effective immune responses to a wide range of antigens. Typically, the target antigen is genetically fused to a hydrophobic protein domain that has been engineered to associate with liposomal membranes. The resulting antigen fusion protein is water soluble under the appropriate conditions, allowing for the isolation and manipulation of the recombinant protein using commercially viable preparative procedures. We have previously shown that this liposomal vaccine complex is highly effective at stimulating active protective immune responses in rodents against viral and bacterial pathogens. However, there is a need for improved adjuvant formulations that can be conveniently modified and used as a tool in vaccine research studies. To address this need, we propose in this SBIR Phase I application to modify our vaccine technology so that a target antigen can simply be chemically coupled to the surface of our liposome without having to produce the recombinant fusion protein. Our central hypothesis is that a highly immunogenic liposome formulation can be prepared that can be easily conjugated with a target antigen chemically and then used as a vaccine. Using Bacillus anthracis, the etiologic agent of anthrax, as a model disease causing pathogen, we have selected two critical target antigens from anthrax to establish the proof of concept for the proposed modification to our vaccine technology. Upon the successful completion of the proposed studies, our modified liposomal vaccine platform technology would then be developed for general sale to the vaccine research community. This would give vaccine researchers an opportunity to take advantage of our antigen delivery system through a kit in which one would simply mix the target antigen with the liposomes in the presence of the appropriate crosslinker, purify the antigen conjugated liposomes if desired, and then use them as a research tool in their vaccination studies. Moreover, liposomal formulations might also be discovered that could be developed into the next generation anthrax vaccine.