Safety of ESAT-6.

A recombinant dimer of the Mycobacterium tuberculosis (MTb) 6kDa early secreted antigenic target (ESAT-6) was produced in Lactococcus lactis. Pharmacodynamic and safety studies were carried out in guinea pigs, rats, mice and dogs with intradermal (id), subcutaneous (sc) and intravenous (iv) administration of the antigen. In contrast to tuberculin purified protein derivative (PPD) the recombinant dimer (rdESAT-6) was able to discriminate MTb infection from BCG vaccination in vivo. In guinea pigs sensitized by infection with MTb, 1μg rdESAT-6 gave a mean delayed-type hypersensitivity (DTH) response of 22mm, a significantly stronger reaction than in animals sensitised by the environmental mycobacteria M. kansasii, M. szulgai and M. marinum. rdESAT-6 proved to be a safe tuberculin reagent in a dose range of 1–1000μg with no or only minor local reactions.