There is an urgent need to develop fast-acting vaccines for biodefense. For pathogens and acute toxins, the ability to rapidly induce immunity with a minimum of adverse effects is of paramount importance. A variety of immunogens from relevant pathogens and toxins have been identified, however numerous immunizations are typically required to induce a protective response. The development of novel adjuvants that boost immune responses without adverse effects is highly desirable. We recently developed a unique reagent that combines the functions of an anthrax antitoxin and vaccine in a single compound. This reagent is based on multivalent display of the anthrax toxin receptor, ANTXR2, on the surface of an icosahedral insect virus. We showed that the recombinant virus-like particles protect rats from anthrax intoxication and that they induce an extremely potent immune response against lethal toxin when coated with anthrax protective antigen (PA). This immune response protects animals against lethal toxin challenge within four weeks after a single administration without the need for adjuvant. The goal of this application is to test whether the utility of this presentation platform can be expanded to display other proteins for which fast-acting vaccines are urgently needed. In particular, we seek to test whether the virus-like particle (VLP) platform can be adapted to generate a rapid and protective immune response to botulinum neurotoxin and ricin toxin.
In aim 1 we will generate PA-RTA and PA-BoNT/A fusion proteins and assemble the VLP-based immunogens.
In aim 2 we will evaluate the immunogenicity of these complexes in vivo. If the proposed strategy is successful, the application of this platform could be expanded dramatically for development of vaccines against numerous other pathogens. (RTA: ricin toxin A chain;BoNT/A: botulinum neurotoxin A).
There is an urgent need to develop fast-acting vaccines for biodefense. We recently developed a unique reagent that induces a protective immune response against anthrax toxin four weeks after a single injection in the absence of an adjuvant. This reagent is based on multivalent display of the anthrax toxin receptor and anthrax protective antigen on the surface of an icosahedral insect virus. The goal of this proposal is to test whether this presentation platform can be used to display other proteins for which fast-acting vaccines are urgently needed. In particular, we seek to test whether the virus-like particle platform can be adapted to generate a rapid and protective immune response to botulinum neurotoxin and ricin toxin. If the proposed strategy is successful, the application of this platform could be expanded dramatically for development of vaccines against numerous other pathogens.
| Venter, P Arno; Dirksen, Anouk; Thomas, Diane et al. (2011) Multivalent display of proteins on viral nanoparticles using molecular recognition and chemical ligation strategies. Biomacromolecules 12:2293-301 |
