Advax-adjuvanted recombinant protective antigen provides protection againstinhalational anthrax that is further enhanced by addition of murabutide adjuvant.

摘要

Subunit vaccines against anthrax based on recombinant protective antigen (PA)potentially offer more consistent and less reactogenic anthrax vaccines butrequire adjuvants to achieve optimal immunogenicity. This study sought todetermine in a murine model of pulmonary anthrax infection whether thepolysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone ortogether could enhance PA immunogenicity by comparison to an alum adjuvant. Asingle immunization with PA plus Advax adjuvant afforded significantly greaterprotection against aerosolized Bacillus anthracis Sterne strain 7702 than threeimmunizations with PA alone. Murabutide had a weaker adjuvant effect than Advaxwhen used alone, but when murabutide was formulated together with Advax, anadditive effect on immunogenicity and protection was observed, with completeprotection after just two doses. The combined adjuvant formulation stimulated arobust, long-lasting B-cell memory response that protected mice against anaerosol challenge 18 months postimmunization with acceleration of the kinetics ofthe anamnestic IgG response to B. anthracis as reflected by ~4-fold-higheranti-PA IgG titers by day 2 postchallenge versus mice that received PA withAlhydrogel. In addition, the combination of Advax plus murabutide inducedapproximately 3-fold-less inflammation than Alhydrogel as measured by in vivoimaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, thecombination of Advax and murabutide provided enhanced protection againstinhalational anthrax with reduced localized inflammation, making this a promisingnext-generation anthrax vaccine adjuvanting strategy.