This study examined the vaccine potential of the autotransporter protein BrkA of Bordetella pertussis in the sublethal intranasal murine respiratory challenge model of infection. Five different acellular pertussis (Pa) vaccines, containing different pertussis-component antigens but all comprizing diphtheria (D) and tetanus (T) toxoids, were tested. A two-pertussis-component DTPa vaccine containing pertussis toxoid (PT) and filamentous hemagglutinin (FHA) induced only limited bacterial clearance. However, a three-pertussis-component DTPa vaccine containing PT, FHA and a recombinant BrkA protein (rBrkA) was found to be as efficacious in protecting mice against colonization by B. pertussis strains Tohama I and 18-323 as the commercial Infanrixtrade mark vaccine that also includes PT and FHA but pertactin (PRN) instead of rBrkA. Vaccination of mice with rBrkA as the only B. pertussis antigen did not protect against colonization by B. pertussis. We also demonstrated that BrkA is ubiquitously expressed by highly prevalent clinical isolates of B. pertussis and suggest that new acellular pertussis vaccine formulations that include BrkA have equivalent efficacy as currently available DTPa vaccines against B. pertussis infections.