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Clin Vaccine Immunol 2014 Apr;21(4):580-6

Advax-adjuvanted Recombinant Protective Antigen Provides Protection Against Inhalational Anthrax That is Further Enhanced by Addition of Murabutide Adjuvant.

Feinen B, Petrovsky N, Verma A, Merkel TJ


Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax™ or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone but when formulated together with Advax, an additive effect on immunogenicity and protection was observed with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months post-immunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ~4-fold higher anti-PA IgG titers by day two post-challenge versus mice that received PA with Alhydrogel. In addition, the Advax plus murabutide combination induced approximately 3-fold less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage by ProSense 750. Thus the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation making this a promising next-generation anthrax vaccine adjuvanting strategy.

Category: Journal Article
PubMed ID: #24554695 DOI: 10.1128/CVI.00019-14
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2013-06-06 Entry Last Modified: 2014-12-15