Anthrax is a highly lethal disease caused by Bacillus anthracis. Currently it poses a major concern as a bioterrorist weapon. The three-component toxin of Bacillus anthracis is the principle mediator of pathogenicity. It consists of the protective antigen (PA), the lethal factor (LF), and the edema factor (EF). Although antibody responses to the PA are known to protect anthrax, a suitable vaccine for prevention of inhalation anthrax, the most lethal form, is not currently available for large-scale practical use. We hypothesize that it might be possible to engineer particular domains of the PA into the hemagglutinin glycoprotein (HA) of influenza virus, and that vaccine strains of influenza containing such chimeric HAs might provide protective immunity against both diseases. One advantage is that influenza vaccines are produced in large scale on an annual basis, so mass immunization procedures would not be problematic provided the recombinant viruses grow reasonably well. Another advantage of this approach relates to the properties of influenza as a strong inducer of both systemic and mucosal immunity, and as such, might enhance the neutralizing antibody responses to PA and provide protection against inhalation anthrax. As such, we propose to generate chimeric HA-PA proteins, assess their capacity to provide HA receptor binding and membrane fusion functions, and generate viruses containing the most suitable constructs by reverse genetics. These viruses will then be analyzed in mice for their ability to induce appropriate anti-HA and anti-PA immune responses.
