Killed Rhabdoviruses as Novel Anthrax Vaccines

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DESCRIPTION (provided by applicant): Anthrax posed only a low risk with minimal natural occurrence in humans until the 20th century, when its development as a bioweapons tool began. Since then, bioterrorism threat using Anthrax is a major risk in the US and abroad and therefore bacillus anthracis has been classified as NIAID Category A Priority Pathogen. As for most infectious diseases, the best strategy against Anthrax is an effective vaccine. However, the existing human vaccine against Anthrax experiences major problems due to a high incidence of toxicity and modest, transient humoral immune responses. The goal of this proposal is the development of an improved human Anthrax vaccine using the novel approach of utilizing a viral capsid (RNP) or virion as a carrier for the Anthrax protective antigen PA. We hypothesize, based on our findings that foreign antigens presented by recombinant rabies virus (RV) ribonucleoprotein (RNP) or virions induce potent humoral responses, that RV-based vectors are also excellent to induce strong and protective B-cell responses against Anthrax. Two different Aims are proposed to address our working hypothesis that RV mediated T-helper response(s) and the presentation of Anthrax protective antigen (PA) to the immune system in a highly organized manner is superior to the use of recombinant Anthrax PA. In the first Aim, chimeric RV nucleoprotein-PA fusion proteins are used as strong B-cell antigens. The second Aim proposes the use of killed RV particles as an efficient vaccine carrier to display anthrax PA protein. For both Aims, we will follow the immune responses in mice vaccinated with various constructs by ELISA, proliferation assays, and in vitro and in vivo toxicity neutralization assays. Lastly, Anthrax challenge experiments of the most promising constructs in mice will indicate if the inducted responses are protective against Anthrax infection.