Preclinical Development of Non-Invasive Anthrax Vaccine

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DESCRIPTION (provided by applicant): The anthrax attacks of 2001 illustrated that the threat of anthrax being used as a weapon of terror on civilians is real. Successful post-exposure treatment of aerosolized anthrax spore exposure requires antibiotic therapy to begin almost immediately and for victims to submit to lengthy antibiotic treatment regimens at compliance levels that have not always proven realistic. A safe, efficacious vaccine that is noninvasive, easy to administer, stimulates innate immune responses against disease almost immediately and that does not have rigid cold-chain requirements offers tremendous advantages for preventing anthrax in the general population. We propose conducting pre-clinical development of a vaccine that is novel by virtue of a non-invasive intranasal delivery route, the development of rapid immune protective responses directed at both the toxin and the B. anthracis bacillus, rapid stimulation of innate immunity and a reduced requirement for cold storage. This vaccine has demonstrated efficacy in protecting rabbits against an aerosol challenge with LD250 spores of virulent Ames anthrax spores. The interim objectives of this application are four-fold. Aim 1) Finalize the vaccine formulation to take forward into development processes. Aim 2) Perform process development, scale up, and qualification leading to contract manufacturing of material suitable for GLP toxicology and animal efficacy studies. Aim 3) Conduct GLP intranasal toxicology in multiple species using the vaccine formulation resulting from Aims 1 and 2. Aim 4) Affirm the efficacy of the vaccine via GLP aerosol challenge of immunized rabbits and primates with virulent anthrax spores. The attainment of these objectives will result in the definition of an intranasally delivered vaccine that is effective at stimulating protection against pulmonary anthrax by both antibody- and cellular-mediated immune responses. It will have a defined manufacturing process, assays for determining that the product is as intended and known safety qualities. This vaccine is expected to require a single dose to elicit protection and to have reduced need for cold storage. It is also expected to stimulate innate immune processes sufficient to protect against an anthrax exposure soon after immunization. The data collected under this grant will cover vaccine efficacy, manufacturing, assaying, stability, and safety, and will position us to submit an Investigational New Drug (IND) application and move into Phase I clinical trials in humans.