Abstract
Studies using the enterotoxin cholera toxin and the related heat-labile toxin I of Escherichia coli as adjuvants have established that effective immunity can be provided in mucosal tissues and the general blood stream by vaccines administered by the oral or nasal route. Despite this knowledge and other recognized advantages, needleless mucosal vaccines rarely appear in the health care market and classic injected vaccines remain the norm. Safety issues related to the adjuvants needed for oral and nasal vaccines are the chief factor that hampers their generalized use in humans. Initial strategies to overcome the toxicity of enterotoxin adjuvants consisted of removing the enzymatic activity of these molecules. The binding of these toxins to their ganglioside receptors was later found to be a major source of safety concern regarding nasal vaccines. Non-ganglioside-binding bacterial toxins and their derivatives are being evaluated as alternatives for the development of effective and safe mucosal vaccines. The CTA1-DD adjuvant, which acts by B-cell targeting of the enzymatically active cholera toxin A subunit, represents one of the strategies to induce immunity by nasal immunization without targeting central nervous system tissues. More recently, we found that the edema toxin of Bacillus anthracis, which binds to target cells via the anthrax toxin receptors and delivers its adenylate cyclase subunit, is an effective adjuvant for nasal vaccines. Interestingly, the unique receptors of anthrax toxin derivatives appear to prevent their accumulation in the central nervous system.
