Immunity to Anthrax

The threat of bioterrorist use of Bacillus anthracis has focused urgent attention on the efficacy and mechanisms of protective immunity induced by the available vaccines. Although numerous humans, and many more animals, are naturally infected every year, the mechanisms of infection-induced immunity have been less well-studied, in part because of difficulties with containment of the virulent pathogen. The Sterne strain, which lacks capsule, is susceptible to complement and is avirulent in animals with an intact complement system. It is, however, fully virulent in animals depleted of complement.

We used a combination of complement depletion along with immunodeficient mice and adoptive transfer approaches to determine the mechanisms of infection-induced protective immunity to B. anthracis. B or T cell-deficient mice lacked the complete anamnestic protection observed in immunocompetent mice. T-cell deficient mice generated poor antibody titers and were protected by the adoptive transfer of antibodies. Adoptively transferred antibodies were also protective in mice lacking complement, FcRs or both, suggesting that they operate independent of these effector functions. Together our data indicates that infection-induced immunity to B. anthracis is via antibody-mediated neutralization.

Our efforts to understand the generation of effective protective immunity to Anthrax are relevant to various measures to protect against this prominent bioterrorism agent.

We have generated a live vaccine with improved characteristics for safely generating effective immunity against a range of pathogens, including those of bioterrorism concern.

• 31. Hughes, M.A., Green, C.S., Lowchyj, L., Lee, G., Grippe, V.K., Smith, Jr., M.F., Huang, C.L., Harvill, E.T and Merkel, T.J. (2005) MyD88-dependent signaling confers protection to Bacillus anthracis spore challenge in mice: Implications for Toll-Like Receptor Signaling. Infection and Immunity 73(11):7535-40.
• 25. Harvill, E.T., Lee, G., Grippe, V.K., and Merkel, T.J. (2005) Complement Depletion Renders C57BL/6 Mice Sensitive to the Bacillus anthracis Sterne Strain. Infection and Immunity, 73(7):4420-2.
• Eric T. Harvill, Manuel Osorio, Gloria Lee, Vanessa K. Grippe, Jenny L. Mellquist, Basil Golding and Tod J. Merkel, Anamnestic Protective Immunity to Bacillus anthracis is Antibody-mediated but Independent of Complement and Fc Receptors. Infection and Immunity. In press.

Dr. Eric Harvill, Veterinary and Biomedical Science
Dr. Harvill previously contributed to the National Academy of Science's National Research Council Committee- Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents. Dr. Harvil currently serves on the National Academy of Science's NRC Committee to Assess the Methodology Used to Calculate the Risk of Bioterrorism.