The predominant antigen in human anthrax vaccines is the protective antigen (PA) of Bacillus anthracis. To address the question whether immune responses against B. anthracis spores can improve the protectivity of a PA-based DNA vaccine against anthrax, we designed a eucaryotic expression plasmid encoding the exosporium antigen BclA, which is a collagen-like surface protein. This plasmid, pSecTag BclA, carries a secretion signal for the recombinant antigen. Using NMRI mice we compared the effects of immunisation with a combination of PA- and BclA-encoding plasmid DNA, to immunisations with either PA- or BclA-encoding pDNA. After three immunisations the mice were infected with 25 x LD(50) of B. anthracis Ames spores. The plasmid pSecTag BclA, induced high BclA-specific antibody responses. Vaccination with a combination of PA- and BclA-encoding pDNA led to significantly better survival than immunisation with only PA- or only BclA-encoding plasmids.