Bioterrorism using anthrax is a major risk in the US and abroad, and, therefore, has been classified as an NIAID Category A Priority Pathogen. The best strategy against anthrax is a safe and effective vaccine. The existing human vaccine against Anthrax has a history of a high incidence of toxicity and modest, transient humoral immune responses. This project proposes the development of a potent Anthrax vaccine by using a viral capsid protein as a carrier for the anthrax protective antigen (PA). Studies have shown that foreign antigens presented to the immune system as fusion proteins with recombinant rabies virus (RV) ribonucleoprotein (RNP), induce more potent humoral responses than when presented as the protein antigens alone. This proposal is based on the overall hypothesis that presentation of anthrax (PA) to the immune system in the highly organized and repetitive manner, as expected for a nucleoprotein fusion protein (Nfu) in RNP, should be superior to the use of monomeric recombinant anthrax PA.
The aims of this project are:
Aim 1 : Test the safety and immunogenicity of recombinant Nfu-PA-RNPs in mice. The existing vaccine, recombinant PA, and E. coli-produced Nfu-PA (monomeric) will serve as controls.
Aim 2 : Assess the ability of sera from Nfu-PA-RNP immunized mice to neutralize toxin in vitro, and to assess the efficacy of the Nfu-PA-RNP vaccine in a mouse Anthrax toxin challenge model and an aerosol Anthrax challenge model.
Aim 3 : Demonstrate feasibility of a purification process for the Nfu-PA-RNPs that consists of conventional scalable methods for potential commercial production. This research is directly relevant to public health in that it is directed towards development of a more effective, less toxic vaccine for a pathogen classified as having the highest threat to national security. The general concept, if proven successful, may also lead to a general technique for developing more effective vaccines for other important pathogens. ? ? ?
| Langley, William A; Bradley, Konrad C; Li, Zhu-Nan et al. (2010) Induction of neutralizing antibody responses to anthrax protective antigen by using influenza virus vectors: implications for disparate immune system priming pathways. J Virol 84:8300-7 |
