Melioidosis is a potentially fatal disease caused by the bacterium, Burkholderia 
pseudomallei. The current study was carried out to determine the mechanisms 
involved in the development of protective immunity in a murine model of 
melioidosis. Following intravenous infection with B. pseudomallei, both C57BL/6 
and BALB/c mice demonstrated delayed-type hypersensitivity responses and 
lymphocyte proliferation towards B. pseudomallei antigens, indicating the 
generation of B. pseudomallei-specific lymphocytes. Adoptive transfer of these 
lymphocytes to naïve C57BL/6 mice was demonstrated by a delayed-type 
hypersensitivity response. Mice were not protected from a subsequent lethal 
challenge with a highly virulent strain of B. pseudomallei, suggesting that a 
single intravenous dose of the bacterium is insufficient to induce a protective 
adaptive immune response. Attempts to induce resistance in susceptible BALB/c 
mice used repetitive low-dose exposure to live B. pseudomallei. Immune responses 
and resistance following subcutaneous immunization with live B. pseudomallei 
were compared with exposure to heat-killed, culture filtrate and sonicated B. 
pseudomallei antigens. Compared to heat-killed B. pseudomallei, significant 
protection was generated in BALB/c mice following immunization with live 
bacteria. Our studies also demonstrate that the type of immune response 
generated in vivo is influenced by the antigenic preparation of B. pseudomallei 
used for immunization.