IAI Accepts, published online ahead of print on 29 December 2008

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Infect. Immun. doi:10.1128/IAI.01217-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Efficacy of a Vaccine Based on Protective Antigen and Killed Spores Against Experimental Inhalational Anthrax

Yves P. Gauthier^*, Jean-Nicolas Tournier, Jean-Charles Paucod, Jean-Philippe Corre, Michèle Mock, Pierre L. Goossens, and Dominique R. Vidal

Département de Biologie des Agents Transmissibles, Centre de Recherches du Service de Santé des Armées Emile Pardé, 38702 La Tronche, France; Unité Toxines et Pathogénie bactérienne, Institut Pasteur, rue du Docteur Roux, CNRS URA 2172, 75015 Paris, France

^* To whom correspondence should be addressed. Email: y_gauthier_crssa{at}yahoo.fr.

PA-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. Several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by PA. Addition of formaldehyde-inactivated spores (FIS) to PA elicits total protection against cutaneous anthrax. Nevertheless, vaccines that are effective against cutaneous anthrax may not be so against inhalational anthrax. The aim of this work was to optimize immunization with PA+FIS, and to assess vaccine efficacy against inhalational anthrax. We assessed the immune response to rPA+FIS administered by various immunization protocols, and the protection provided to mice and guinea pigs infected through the respiratory route with spores of a virulent strain of B. anthracis. Combined subcutaneous plus intranasal immunization of mice yielded a mucosal IgG response to rPA that was more than 20 times higher than that in lung mucosal secretions after subcutaneous vaccination. The titers of toxin-neutralizing antibody and anti-spore antibody were also significantly higher: nine and eight times higher respectively. The optimized immunization elicited total protection of mice intranasally infected with the virulent B. anthracis strain 17JB. Guinea pigs were fully protected, both against an intranasal challenge with 100 LD₅₀ and against an aerosol with 75 LD₅₀ of spores of the highly virulent strain 9602. Conversely, immunization with PA alone did not elicit protection. These results demonstrate that the association of PA and spores is very much more effective than PA alone against experimental inhalational anthrax.