Increasing knowledge about DosR regulon-encoded proteins has led us to produce 
novel Mycobacterium tuberculosis antigens for immunogenicity testing in human 
populations in three countries in Africa to which tuberculosis (TB) is endemic. 
A total of 131 tuberculin skin test-positive and/or ESAT-6/CFP10-positive, human 
immunodeficiency virus-negative adult household contacts of active pulmonary TB 
cases from South Africa (n = 56), The Gambia (n = 26), and Uganda (n = 49) were 
tested for gamma interferon responses to 7 classical and 51 DosR regulon-encoded 
M. tuberculosis recombinant protein antigens. ESAT-6/CFP10 fusion protein evoked 
responses in >75% of study participants in all three countries. Of the DosR 
regulon-encoded antigens tested, Rv1733c was the most commonly recognized by 
participants from both South Africa and Uganda and the third most commonly 
recognized antigen in The Gambia. The four most frequently recognized DosR 
regulon-encoded antigens in Uganda (Rv1733c, Rv0081, Rv1735c, and Rv1737c) 
included the three most immunogenic antigens in South Africa. In contrast, 
Rv3131 induced the highest percentage of responders in Gambian contacts (38%), 
compared to only 3.4% of Ugandan contacts and no South African contacts. 
Appreciable percentages of TB contacts with a high likelihood of latent M. 
tuberculosis infection responded to several novel DosR regulon-encoded M. 
tuberculosis proteins. In addition to significant similarities in antigen 
recognition profiles between the three African population groups, there were 
also disparities, which may stem from genetic differences between both pathogen 
and host populations. Our findings have implications for the selection of 
potential TB vaccine candidates and for determining biosignatures of latent M. 
tuberculosis infection, active TB disease, and protective immunity.